Wojciech Paslawski

Wojciech Paslawski

Karolinska Institutet

H-index: 10

Europe-Sweden

About Wojciech Paslawski

Wojciech Paslawski, With an exceptional h-index of 10 and a recent h-index of 10 (since 2020), a distinguished researcher at Karolinska Institutet, specializes in the field of Biophysics, Neuroscience, Proteins.

His recent articles reflect a diverse array of research interests and contributions to the field:

Novel α-Synuclein Fibrils PET tracers in PFF Mouse Model of Parkinson’s Disease

Maternal deprivation causes CaMKII downregulation and modulates glutamate, norepinephrine and serotonin in limbic brain areas in a rat model of single prolonged stress

Secretome Analyses Identify FKBP4 as a GBA1-Associated Protein in CSF and iPS Cells from Parkinson’s Disease Patients with GBA1 Mutations

Gut-Initiated Alpha Synuclein Fibrils Drive Parkinson's Disease Phenotypes: Temporal Mapping of non-Motor Symptoms and REM Sleep Behavior Disorder

Elevated ApoE, ApoJ and lipoprotein-bound α-synuclein levels in cerebrospinal fluid from Parkinson's disease patients–Validation in the BioFIND cohort

Large-scale proximity extension assay reveals CSF midkine and DOPA decarboxylase as supportive diagnostic biomarkers for Parkinson’s disease

Selective α-Synuclein PET Radiotracer Development-Characterization

Single-cell transcriptomics reveals correct developmental dynamics and high-quality midbrain cell types by improved hESC differentiation

Wojciech Paslawski Information

University

Karolinska Institutet

Position

___

Citations(all)

725

Citations(since 2020)

474

Cited By

414

hIndex(all)

10

hIndex(since 2020)

10

i10Index(all)

11

i10Index(since 2020)

11

Email

University Profile Page

Karolinska Institutet

Wojciech Paslawski Skills & Research Interests

Biophysics

Neuroscience

Proteins

Top articles of Wojciech Paslawski

Novel α-Synuclein Fibrils PET tracers in PFF Mouse Model of Parkinson’s Disease

Authors

B Hooshyar Yousefi,B Uzuegbunam,S Bagheri,J Li,W Paslawski,P Svenningsson,H Agren,T Arzberger,M Luster,W Weber,D Librizzi

Journal

Nuklearmedizin-NuclearMedicine

Published Date

2024/4

Ziel/Aim: The role of α-synuclein fibrils (α-syn) in the pathogenesis of neurodegenerative disorders collectively known as the α-synucleinopathies represents a milestone in the in vivo detection of α-syn, such as Lewy bodies and Lewy neurites as an early diagnosis in α-synucleinopathies including idiopathic PD, DLB, MSA, pure autonomic failure and REM sleep behavior disorder. Four selected 4, 4-Disarylbisthiazole (DABTA) based radiotracers under went in vivo and in vitro study for their affinity to α-syn, selectivity over tau and Aβ using animal models and postmortem brains.Methodik/Methods: Four novel DABTAs based on in silico, binding and pharmacokinetics results were selected and utilized as tracer with nca F-18 labeling for PET in mouse models through the 12 weeks post intrastriatal introduction of pathological α-syn seeds in the form of preformed fibrils (PFF) vs control. The binding assays, metabolite …

Maternal deprivation causes CaMKII downregulation and modulates glutamate, norepinephrine and serotonin in limbic brain areas in a rat model of single prolonged stress

Authors

Đorđe Đorović,Vesna Lazarevic,Jovana Aranđelović,Vladimir Stevanović,Wojciech Paslawski,Xiaoqun Zhang,Milica Velimirović,Nataša Petronijević,Laslo Puškaš,Miroslav M Savić,Per Svenningsson

Journal

Journal of Affective Disorders

Published Date

2024/3/15

BackgroundEarly life stress is a major risk factor for later development of psychiatric disorders, including post-traumatic stress disorder (PTSD). An intricate relationship exists between various neurotransmitters (such as glutamate, norepinephrine or serotonin), calcium/calmodulin-dependent protein kinase II (CaMKII), as an important regulator of glutamatergic synaptic function, and PTSD. Here, we developed a double-hit model to investigate the interaction of maternal deprivation (MD) as an early life stress model and single prolonged stress (SPS) as a PTSD model at the behavioral and molecular levels.MethodsMale Wistar rats exposed to these stress paradigms were subjected to a comprehensive behavioral analysis. In hippocampal synaptosomes we investigated neurotransmitter release and glutamate concentration. The expression of CaMKII and the content of monoamines were determined in selected brain …

Secretome Analyses Identify FKBP4 as a GBA1-Associated Protein in CSF and iPS Cells from Parkinson’s Disease Patients with GBA1 Mutations

Authors

Rika Kojima,Wojciech Paslawski,Guochang Lyu,Ernest Arenas,Xiaoqun Zhang,Per Svenningsson

Journal

International Journal of Molecular Sciences

Published Date

2024/1/4

Mutations in the GBA1 gene increase the risk of developing Parkinson’s disease (PD). However, most carriers of GBA1 mutations do not develop PD throughout their lives. The mechanisms of how GBA1 mutations contribute to PD pathogenesis remain unclear. Cerebrospinal fluid (CSF) is used for detecting pathological conditions of diseases, providing insights into the molecular mechanisms underlying neurodegenerative disorders. In this study, we utilized the proximity extension assay to examine the levels of metabolism-linked protein in the CSF from 17 PD patients carrying GBA1 mutations (GBA1-PD) and 17 idiopathic PD (iPD). The analysis of CSF secretome in GBA1-PD identified 11 significantly altered proteins, namely FKBP4, THOP1, GLRX, TXNDC5, GAL, SEMA3F, CRKL, APLP1, LRP11, CD164, and NPTXR. To investigate GBA1-associated CSF changes attributed to specific neuronal subtypes responsible for PD, we analyzed the cell culture supernatant from GBA1-PD-induced pluripotent stem cell (iPSC)-derived midbrain dopaminergic (mDA) neurons. The secretome analysis of GBA1-PD iPSC-derived mDA neurons revealed that five differently regulated proteins overlapped with those identified in the CSF analysis: FKBP4, THOP1, GLRX, GAL, and CRKL. Reduced intracellular level of the top hit, FKPB4, was confirmed via Western Blot. In conclusion, our findings identify significantly altered CSF GBA1-PD-associated proteins with FKPB4 being firmly attributed to mDA neurons.

Gut-Initiated Alpha Synuclein Fibrils Drive Parkinson's Disease Phenotypes: Temporal Mapping of non-Motor Symptoms and REM Sleep Behavior Disorder

Authors

Daniel Dautan,Wojciech Paslawski,Sergio Montejo,Daniel Doyon,Roberta Marangiu,Michael G Kaplitt,Rong Chen,Valina L Dawson,Xiaoqun Zhang,Ted M Dawson,Per Svenningsson

Journal

bioRxiv

Published Date

2024

Parkinson's disease (PD) is characterized by progressive motor as well as less recognized non-motor symptoms that arise often years before motor manifestation, including sleep and gastrointestinal disturbances. Despite the heavy burden on the patient's quality of life, these non-motor manifestations are poorly understood. To elucidate the temporal dynamics of the disease, we employed a mouse model involving injection of alpha-synuclein (aSyn) pre-formed fibrils (PFF) in the duodenum and antrum as a gut-brain model of Parkinsonism. Using anatomical mapping of aSyn-PFF propagation and behavioral and physiological characterizations, we unveil a correlation between post-injection time the temporal dynamics of aSyn propagation and non-motor/motor manifestations of the disease. We highlight the concurrent presence of aSyn aggregates in key brain regions, expressing acetylcholine or dopamine, involved in sleep duration, wakefulness, and particularly REM-associated atonia corresponding to REM behavioral disorder-like symptoms. This study presents a novel and in-depth exploration into the multifaceted nature of PD, unraveling the complex connections between aSynucleinopathies, gut-brain connectivity, and the emergence of non-motor phenotypes.

Elevated ApoE, ApoJ and lipoprotein-bound α-synuclein levels in cerebrospinal fluid from Parkinson's disease patients–Validation in the BioFIND cohort

Authors

Wojciech Paslawski,Per Svenningsson

Journal

Parkinsonism & Related Disorders

Published Date

2023/11/1

BackgroundThe progressive accumulation, aggregation, and spread of α-synuclein (aSN) are common hallmarks of Parkinson's disease (PD) pathology. The genotype of apolipoprotein E (ApoE) influences PD progression. Recently we found that aSN co-localize with apolipoproteins on lipoprotein vesicles. We reported an increased level of ApoE, ApoJ and lipoprotein-bound aSN in CSF from early PD patients compared to matched controls. We also found reduced plasma ApoAI in PD patients.ObjectiveIn this study, we used the same approach on the BioFIND cohort to validate our previous results and extended the studies to examine correlations with ApoE genotype, demographic variables, clinical symptoms and other biochemical findings reported in the BioFIND cohort.MethodsFor the assessment, we used Western-Blot (WB) technique for apolipoproteins measurements in CSF and plasma from PD patients and …

Large-scale proximity extension assay reveals CSF midkine and DOPA decarboxylase as supportive diagnostic biomarkers for Parkinson’s disease

Authors

Wojciech Paslawski,Shervin Khosousi,Ellen Hertz,Ioanna Markaki,Adam Boxer,Per Svenningsson

Journal

Translational Neurodegeneration

Published Date

2023/9/4

BackgroundThere is a need for biomarkers to support an accurate diagnosis of Parkinson’s disease (PD). Cerebrospinal fluid (CSF) has been a successful biofluid for finding neurodegenerative biomarkers, and modern highly sensitive multiplexing methods offer the possibility to perform discovery studies. Using a large-scale multiplex proximity extension assay (PEA) approach, we aimed to discover novel diagnostic protein biomarkers allowing accurate discrimination of PD from both controls and atypical Parkinsonian disorders (APD).MethodsCSF from patients with PD, corticobasal syndrome (CBS), progressive supranuclear palsy (PSP), multiple system atrophy and controls, were analysed with Olink PEA panels. Three cohorts were used in this study, comprising 192, 88 and 36 cases, respectively. All samples were run on the Cardiovascular II, Oncology II and Metabolism PEA panels.ResultsOur analysis …

Selective α-Synuclein PET Radiotracer Development-Characterization

Authors

B Hooshyar Yousefi,BC Uzuegbunam,W Paslawski,GB Kotipalli,M Luster,D Librizzi,W Weber,P Svenningsson,T Arzberger

Journal

Nuklearmedizin-NuclearMedicine

Published Date

2023/4

Ziel/Aim The deposition of α-synuclein fibrils (α-syn) is a major feature that unites a group of neurodegenerative diseases collectively known as the synucleinopathies. Presently, the in vivo detection of this biomarker is not possible due to lack of suitable radiotracers. Scientists from academics and industry are interested to develop radiotracers for the early diagnosis of α-synucleinopathies. Disarylbisthiazoles (DABTAs) based ligands have been showing high affinity towards α-syn and excellent selectivity over tau and Aβ aggregates. The aim of this work is characterization of the radiotracers within competition binding assays, autoradiography and pharmacokinetics (PK) study to confirm their high binding affinity and optimized pharmacokinetics and utilize them as a promising α-syn PET tracer.Methodik/Methods A library of fifty DABTAs were synthesized and studied in competition binding assays. The selected …

Single-cell transcriptomics reveals correct developmental dynamics and high-quality midbrain cell types by improved hESC differentiation

Authors

Kaneyasu Nishimura,Shanzheng Yang,Kawai Lee,Emilia Sif Asgrimsdottir,Kasra Nikouei,Wojciech Paslawski,Sabine Gnodde,Guochang Lyu,Lijuan Hu,Carmen Salto,Per Svenningsson,Jens Hjerling-Leffler,Sten Linnarsson,Ernest Arenas

Journal

bioRxiv

Published Date

2022/1/1

Stem cell technologies provide new opportunities for modeling cells in health and disease and for regenerative medicine. In both cases, developmental knowledge and defining the molecular properties and quality of the cell types is essential. In this study, we identify developmental factors important for the differentiation of human embryonic stem cells (hESCs) into functional midbrain dopaminergic (mDA) neurons. We found that laminin-511, and dual canonical and non-canonical WNT activation followed by GSK3β inhibition plus FGF8b, improved midbrain patterning. In addition, neurogenesis and differentiation were enhanced by activation of liver X receptors and inhibition of fibroblast growth factor signaling. Moreover, single-cell RNA-sequencing analysis revealed a developmental dynamics similar to that of the endogenous human ventral midbrain and the emergence of high-quality molecularly defined midbrain …

Sequestrins inhibiting amyloidogenic aggregation-prone peptides

Authors

Linnea C Hjelm,Hanna Lindberg,Wojciech Paslawski,Per Svenningsson,Stefan Ståhl,John Löfblom

Published Date

2023

Neurodegenerative disorders include a full spectrum of diagnoses, including dementias and other neuronal diseases, characterised by degradation of neurons in the brain occurring along with disease progression. Amongst the dementias, the most prevalent are Alzheimer’s (AD) and Parkinson’s disease (PD) that affect millions of people worldwide. During the last years, advancements in potential treatments have been made where the first two clinical antibodies have been approved by the US Food and Drug Administration (FDA) for a disease modifying effect on Alzheimer’s disease.As alternatives to antibodies, other types of affinity reagents that are based on non-immunoglobulin protein scaffolds are also investigated. Such alternative scaffolds often demonstrate distinct and complementary properties compared to antibodies. In this thesis, the development of a new type of affinity protein scaffold called sequestrin is described. Sequestrins are derived from the affibody molecule and comprise two heterogenic subunits with truncated N-terminals fused as a head-to-tail construct. Sequestrins undergo a structural rearrangement upon target binding and forms a stabile complex. The scaffold is designed for interactions with disease-related amyloidogenic peptides eg amyloid beta and alpha-synuclein involved in AD and PD, respectively. In the first paper, a sequestrin library was developed and its compatibility with phage display was investigated. Successful panning against the amyloid beta peptide resulted in binders with high affinity. Further on in paper II, the alpha-synuclein peptide was targeted and sequestrins with low nanomolar affinities were …

In Silico and In Vitro Study towards the Rational Design of 4, 4′-Disarylbisthiazoles as a Selective α-Synucleinopathy Biomarker

Authors

Bright C Uzuegbunam,Junhao Li,Wojciech Paslawski,Wolfgang Weber,Per Svenningsson,Hans Ågren,Behrooz Hooshyar Yousefi

Journal

International Journal of Molecular Sciences

Published Date

2023/11/17

The α-synucleinopathies are a group of neurodegenerative diseases characterized by the deposition of α-synuclein aggregates (α-syn) in the brain. Currently, there is no suitable tracer to enable a definitive early diagnosis of these diseases. We reported candidates based on 4,4′-disarylbisthiazole (DABTA) scaffold with a high affinity towards α-syn and excellent selectivity over Aβ and tau fibrils. Based on prior in silico studies, a focused library of 23 halogen-containing and O-methylated DABTAs was prepared. The DABTAs were synthesized via a modified two-step Hantzsch thiazole synthesis, characterized, and used in competitive binding assays against [3H]PiB and [3H]DCVJ. The DABTAs were obtained with an overall chemical yield of 15–71%, and showed a calculated lipophilicity of 2.5–5.7. The ligands demonstrated an excellent affinity to α-syn with both [3H]PiB and [3H]DCVJ: Ki 0.1–4.9 nM and up to 20–3900-fold selectivity over Aβ and tau fibrils. It could be concluded that in silico simulation is useful for the rational design of a new generation of DABTAs. Further investigation of the leads in the next step is encouraged: radiolabeling of the ligands with radioisotopes such as fluorine-18 or carbon-11 for in vivo, ex vivo, and translational research and for further in vitro experiments on human-derived protein aggregates.

Isolation of L1CAM‐Extracellular Vesicles Reveals Signs of Insulin Resistance in Parkinson's Disease

Authors

Ioanna Markaki,Wojciech Paslawski,Theodora Ntetsika,Lisa Engesvik,Sergiu‐Bogdan Catrina,Per Svenningsson

Journal

Movement Disorders

Published Date

2023/11

Similar molecular processes have been identified in the development of Parkinson’s disease (PD) and type 2 diabetes mellitus (T2DM). 1 Insulin resistance is a central feature of T2DM pathology, and recent evidence supports its occurrence in the brain and its contribution in neurodegeneration. 2Insulin receptor substrate (IRS)-1 is the initial node in the pathway of insulin signaling and its activity is modified through phosphorylation of specific tyrosine (activation) and serine (inhibition) residues. 3 L1 cell adhesion molecule (L1CAM) extracellular vesicles (EVs) in plasma have been suggested as potential markers of neuronal origin, 4 which may provide a non-invasive method to assess brain insulin resistance in PD. 5 Here, we present evidence independent from the research group that originally developed the L1CAM-EVs method, supporting the presence of brain insulin resistance in PD. In total, 80 persons with …

PRC2-mediated repression is essential to maintain identity and function of differentiated dopaminergic and serotonergic neurons

Authors

Konstantinos Toskas,Behzad Yaghmaeian-Salmani,Olga Skiteva,Wojciech Paslawski,Linda Gillberg,Vasiliki Skara,Irene Antoniou,Erik Södersten,Per Svenningsson,Karima Chergui,Markus Ringnér,Thomas Perlmann,Johan Holmberg

Journal

Science Advances

Published Date

2022/8/26

How neurons can maintain cellular identity over an entire life span remains largely unknown. Here, we show that maintenance of identity in differentiated dopaminergic and serotonergic neurons is critically reliant on the Polycomb repressive complex 2 (PRC2). Deletion of the obligate PRC2 component, Eed, in these neurons resulted in global loss of H3K27me3, followed by a gradual activation of genes harboring both H3K27me3 and H3K9me3 modifications. Notably, H3K9me3 was lost at these PRC2 targets before gene activation. Neuronal survival was not compromised; instead, there was a reduction in subtype-specific gene expression and a progressive impairment of dopaminergic and serotonergic neuronal function, leading to behavioral deficits characteristic of Parkinson’s disease and anxiety. Single-cell analysis revealed subtype-specific vulnerability to loss of PRC2 repression in dopamine neurons of the …

α-Synuclein induced cholesterol lowering increases tonic and reduces depolarization-evoked synaptic vesicle recycling and glutamate release

Authors

Vesna Lazarevic,Yunting Yang,Wojciech Paslawski,Per Svenningsson

Journal

npj Parkinson's Disease

Published Date

2022/6/7

α-Synuclein (α-syn) is a key molecule linked to Parkinson’s disease pathology. Physiologically, the monomeric α-syn in the presynaptic termini is involved in regulation of neurotransmission, but the pathophysiology of extracellular monomeric α-syn is still unknown. Utilizing both in vivo and in vitro approaches, we investigated how extracellular α-syn impact presynaptic structure and function. Our data revealed that treatment with exogenous α-syn leads to increased tonic and decreased depolarization-evoked synaptic vesicle (SV) recycling and glutamate release. This was associated with mobilization of molecularly distinct SV pools and reorganization of active zone components. Our study also showed that exogenous α-syn impaired neuronal cholesterol level and that the cholesterol binding domain of α-syn was sufficient to exert the same presynaptic phenotype as the full-length protein. The present study sheds …

Toward Novel [18F] Fluorine-labeled radiotracers for the imaging of α-synuclein fibrils

Authors

Bright C Uzuegbunam,Junhao Li,Wojciech Paslawski,Wolfgang Weber,Per Svenningsson,Hans Ågren,Behrooz Hooshyar Yousefi

Journal

Frontiers in Aging Neuroscience

Published Date

2022/4/29

The accumulation of α-synuclein aggregates (α syn) in the human brain is an occurrence common to all α-synucleinopathies. Non-invasive detection of α syn in a living brain with a radiotracer is not yet possible. We have recently discovered that a methylenedioxy group in the structure of diarylbisthiazole (DABTA) based tracers improves binding affinity and selectivity to α-syn. Subsequently, complementary in–silico modelling and machine learning (ML) of tracer-protein interaction were employed to predict surface sites and structure-property rela-tions for the binding of the ligands. Based on this we developed a small focused library of DABTAs from which 4-(benzo[d][1,3]dioxol-5-yl)-4'-(3-[18F]fluoro-4-methoxyphenyl)-2,2'-bithiazole [18F]d2, 6-(4'-(3-[18F]fluoro-4-methoxyphenyl)-[2,2'-bithiazol]-4-yl)-[1,3]dioxolo[4,5-b]pyridine [18F]d4, 4-(benzo [d][1,3]dioxol-5-yl)-4'-(6-[18F]fluoropyridin-3-yl)-2,2'-bithiazole [18F]d6, 6-(4'-(6-[18F]fluoropyridin-3-yl)-[2,2'-bithiazol]-4-yl)-[1,3]dioxolo[4,5-b]pyridine [18F]d8 were selected based on their high binding affinity and further evaluated. Binding assays carried out with the non-radioactive d2, d4, d6 and d8 showed high binding affinity to α-syn: 1.22, 0.66, 1.21 and 0.10 nM respectively as well as excellent selectivity over β-amyloid plaques (Aβ) and microtubular tau aggregates (> 200-fold selectivity). To obtain the tracers, their precursors were radiolabeled either via an innovative ruthenium-mediated reaction ([18F]d2 and [18F]d4) or typical SNAr reaction ([18F]d6 and [18F]d8) with moderate to high radiochemical yields (13 %-40 %), and high molar activity > 60 GBq/μmol. Biodistribution experiments carried out with …

High Affinity Radiopharmaceuticals for Alpha-synuclein Aggregates with Improved Pharmacokinetics

Authors

B Hooshyar Yousefi,BC Uzuegbunam,W Paslawski,Y Zhou,M Luster,P Svenningsson,H Ågren,W Weber

Journal

Nuklearmedizin-NuclearMedicine

Published Date

2022/4

Ziel/Aim Development and evaluation of high affinity 18 F-labeled radiopharmaceuticals for Alpha-synuclein Aggregates (α-syn) with improved pharmacokinetics based on disarybisthiazoles (DABTA) to α-synuclein fibrils with excellent selectivity over β-amyloid (Aβ) and tau (τ) fibrils.Methodik/Methods Improved tracers with high affinity to α-syn with excellent selectivity and suitable brain uptake kinetics identified ligands with improved pharmacokinetics and in vivo stability were developed. The ligands were synthesized via a modified Hantzsch thiazole synthesis, and radiofluorinated via nca one-or two-step radiofluorination. Molecular dynamics and quantum/molecular mechanics approaches were applied to calculate the binding. Machine learning methods (MLM) were used to model the physiochemical properties and pharmacokinetics of the ligands. The ligands were further screened via experimental lipophilicity …

Impaired Aversive Memory Formation in GPR37L1KO Mice

Authors

Vandana Veenit,Xiaoqun Zhang,Wojciech Paslawski,Ioannis Mantas,Per Svenningsson

Journal

International Journal of Molecular Sciences

Published Date

2022/11/18

GPR37L1 is an orphan G-protein-coupled receptor, which is implicated in neurological disorders, but its normal physiological role is poorly understood. Its close homologue, GPR37, is implicated in Parkinson’s disease and affective disorders. In this study, we set out to characterize adult and middle-aged global GPR37L1 knock-out (KO) mice regarding emotional behaviors. Our results showed that GPR37L1KO animals, except adult GPR37L1KO males, exhibited impaired retention of aversive memory formation as assessed by the shorter retention latency in a passive avoidance task. Interestingly, the viral-mediated deletion of GPR37L1 in conditional knockout mice in the hippocampus of middle-aged mice also showed impaired retention in passive avoidance tasks, similar to what was observed in global GPR37L1KO mice, suggesting that hippocampal GPR37L1 is involved in aversive learning processes. We also observed that middle-aged GPR37L1KO male and female mice exhibited a higher body weight than their wild-type counterparts. Adult and middle-aged GPR37L1KO female mice exhibited a reduced level of serum corticosterone and middle-aged GPR37L1KO females showed a reduced level of epinephrine in the dorsal hippocampus in the aftermath of passive avoidance task, with no such effects observed in GPR37L1KO male mice, suggesting that lack of GPR37L1 influences behavior and biochemical readouts in age- and sex-specific manners.

Prosaposin reduces α-Synuclein in cells and Saposin C dislodges it from glucosylceramide-enriched lipid membranes

Authors

Rika Kojima,Mark Zurbruegg,Tianyi Li,Wojciech Paslawski,Xiaoqun Zhang,Per Svenningsson

Journal

Journal of Molecular Neuroscience

Published Date

2022/11

Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder affecting over 1% of the 65 + age population. Saposin C, a lysosomal protein required for the normal activity of glucocerebrosidase (GCase), may serve as a disease modifier in PD. Saposin C is cleaved from its precursor, Prosaposin (PSAP), which is secreted as an uncleaved protein and exerts neuroprotective effects. In this study, we aim to elucidate the neuroprotective roles of PSAP and saposin C in PD by evaluating their effects on α-synuclein accumulation in human neuroblastoma cells. Stable overexpression of PSAP reduced monomeric α-synuclein levels in SH-SY5Y cells, while PSAP knockdown by small interfering RNA led to the opposite effect, and those effects were independent of GCase activity. Autophagy flux was decreased by stable PSAP overexpression. Furthermore, a flow-through assay revealed …

Optimized disarybisthiazole derivatives with high affinity to alpha-synuclein aggregates and improved pharmacokinetics

Authors

BC Uzuegbunam,W Paslawski,Y Zhou,H Ågren,B Längström,WA Weber,BH Yousefi

Journal

Nuklearmedizin-NuclearMedicine

Published Date

2021/4

Ziel/Aim To optimize the pharmacokinetics, and the binding affinity of F-18-labeled disarybisthiazoles (DABTAs) to α-synuclein (α-syn) fibrils and selectivity over β-amyloid (A β) and tau (τ) fibrils which might co-exist with our target.Methodik/Methods Following the development of tracers with high affinity to α-syn relative to the other amyloid fibrils, but unfortunately slow clearance from normal brain tissues, we identified ligands with improved hydrophilicity. The ligands were radiofluorinated via nca one-or two-step radiofluorination. A combination of molecular dynamics and quantum/molecular mechanics approaches were applied to calculate their binding. Machine learning methods were used to model the physiochemical properties and pharmacokinetics of the ligands. The ligands were further screened via experimental logD & binding assays, plasma stability, biodistribution and brain metabolite analyzes.

Ecto-GPR37: A potential biomarker for Parkinson’s disease

Authors

Xavier Morató,Paula Garcia-Esparcia,Josep Argerich,Franc Llorens,Inga Zerr,Wojciech Paslawski,Eva Borràs,Eduard Sabidó,Ulla E Petäjä-Repo,Víctor Fernández-Dueñas,Isidro Ferrer,Per Svenningsson,Francisco Ciruela

Journal

Translational neurodegeneration

Published Date

2021/12

Objective α-Synuclein has been studied as a potential biomarker for Parkinson’s disease (PD) with no concluding results. Accordingly, there is an urgent need to find out reliable specific biomarkers for PD. GPR37 is an orphan G protein-coupled receptor that toxically accumulates in autosomal recessive juvenile parkinsonism. Here, we investigated whether GPR37 is upregulated in sporadic PD, and thus a suitable potential biomarker for PD. Methods GPR37 protein density and mRNA expression in postmortem substantia nigra (SN) from PD patients were analysed by immunoblot and RT-qPCR, respectively. The presence of peptides from the N-terminus-cleaved domain of GPR37 (i.e. ecto-GPR37) in human cerebrospinal fluid (CSF) was determined by liquid chromatography-mass spectrometric analysis. An engineered in-house nanoluciferase-based …

P11 deficiency increases stress reactivity along with HPA axis and autonomic hyperresponsiveness

Authors

Vasco C Sousa,Ioannis Mantas,Nikolas Stroth,Torben Hager,Marcela Pereira,Haitang Jiang,Sandra Jabre,Wojciech Paslawski,Oliver Stiedl,Per Svenningsson

Journal

Molecular psychiatry

Published Date

2021/7

Patients suffering from mood disorders and anxiety commonly exhibit hypothalamic–pituitary–adrenocortical (HPA) axis and autonomic hyperresponsiveness. A wealth of data using preclinical animal models and human patient samples indicate that p11 deficiency is implicated in depression-like phenotypes. In the present study, we used p11-deficient (p11KO) mice to study potential roles of p11 in stress responsiveness. We measured stress response using behavioral, endocrine, and physiological readouts across early postnatal and adult life. Our data show that p11KO pups respond more strongly to maternal separation than wild-type pups, even though their mothers show no deficits in maternal behavior. Adult p11KO mice display hyperactivity of the HPA axis, which is paralleled by depression- and anxiety-like behaviors. p11 was found to be highly enriched in vasopressinergic cells of the paraventricular nucleus …

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What is Wojciech Paslawski's h-index at Karolinska Institutet?

The h-index of Wojciech Paslawski has been 10 since 2020 and 10 in total.

What are Wojciech Paslawski's top articles?

The articles with the titles of

Novel α-Synuclein Fibrils PET tracers in PFF Mouse Model of Parkinson’s Disease

Maternal deprivation causes CaMKII downregulation and modulates glutamate, norepinephrine and serotonin in limbic brain areas in a rat model of single prolonged stress

Secretome Analyses Identify FKBP4 as a GBA1-Associated Protein in CSF and iPS Cells from Parkinson’s Disease Patients with GBA1 Mutations

Gut-Initiated Alpha Synuclein Fibrils Drive Parkinson's Disease Phenotypes: Temporal Mapping of non-Motor Symptoms and REM Sleep Behavior Disorder

Elevated ApoE, ApoJ and lipoprotein-bound α-synuclein levels in cerebrospinal fluid from Parkinson's disease patients–Validation in the BioFIND cohort

Large-scale proximity extension assay reveals CSF midkine and DOPA decarboxylase as supportive diagnostic biomarkers for Parkinson’s disease

Selective α-Synuclein PET Radiotracer Development-Characterization

Single-cell transcriptomics reveals correct developmental dynamics and high-quality midbrain cell types by improved hESC differentiation

...

are the top articles of Wojciech Paslawski at Karolinska Institutet.

What are Wojciech Paslawski's research interests?

The research interests of Wojciech Paslawski are: Biophysics, Neuroscience, Proteins

What is Wojciech Paslawski's total number of citations?

Wojciech Paslawski has 725 citations in total.

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