Synucleins are small naturally unfolded proteins involved in neurodegenerative diseases and cancer. The family contains three members: α-, β-, and -synuclein. α-Synuclein is the most thoroughly investigated because of its close association with Parkinson's disease (PD), dementia with Lewy bodies and multiple system atrophy. Until recently, the synuclein's research was mainly focused on their intracellular forms. However, new studies highlighted the important role of extracellular synucleins. Extracellular forms of synucleins propagate between various types of cells, bind to cell surface receptors and transmit signals, regulating numerous intracellular processes. Here we give an update of the latest results about the mechanisms of action of extracellular synucleins, their binding to cell surface receptors, effect on biochemical pathways and the role in neurodegeneration and neuroinflammation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359176 | PMC |
| http://dx.doi.org/10.3390/molecules24020305 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Correction for Gilboa et al., Measurement of α-synuclein as protein cargo in plasma extracellular vesicles.
Proc Natl Acad Sci U S A
February 2025
Alpha-synuclein inhibits the secretion of extracellular vesicles through disruptions in YKT6 lipidation.
J Neurosci
January 2025
Department of Neurology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Parkinson's disease is characterized by the presence of α-synuclein (α-syn) primarily containing Lewy bodies in neurons. Despite decades of extensive research on α-syn accumulation, its molecular mechanisms have remained largely unexplored. Recent studies by us and others have suggested that extracellular vesicles (EVs), especially exosomes, can mediate the release of α-syn from cells, and inhibiting this pathway could result in increased intracellular α-syn levels.
View Article and Find Full Text PDFMicroglia depletion reduces neurodegeneration and remodels extracellular matrix in a mouse Parkinson's disease model triggered by α-synuclein overexpression.
NPJ Parkinsons Dis
January 2025
Department of Neurobiology, Center of Parkinson Disease Beijing Institute for Brain Disorders, Beijing Key Laboratory on Parkinson Disease, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University, Beijing, 100069, China.
Chronic neuroinflammation with sustained microglial activation occurs in Parkinson's disease (PD), yet the mechanisms and exact contribution of these cells to the neurodegeneration remains poorly understood. In this study, we induced progressive dopaminergic neuron loss in mice via rAAV-hSYN injection to cause the neuronal expression of α-synuclein, which produced neuroinflammation and behavioral alterations. We administered PLX5622, a colony-stimulating factor 1 receptor inhibitor, for 3 weeks prior to rAAV-hSYN injection, maintaining it for 8 weeks to eliminate microglia.
View Article and Find Full Text PDFIntracellular α-synuclein assemblies are sufficient to alter nanoscale diffusion in the striatal extracellular space.
NPJ Parkinsons Dis
December 2024
Univ. Bordeaux, CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000, Bordeaux, France.
α-synucleinopathies progression involves the spread of α-synuclein aggregates through the extracellular space (ECS). Single-particle tracking studies showed that α-synuclein-induced neurodegeneration increases ECS molecular diffusivity. To disentangle the consequences of neuronal loss versus α-synuclein-positive intracellular assemblies formation, we performed near-infrared single-particle tracking to characterise ECS rheology in the striatum of mouse models of α-synucleinopathies.
View Article and Find Full Text PDFAlzheimer's disease (AD) is a progressive neurodegenerative disorder, characterized by the presence of extracellular amyloid plaques consisting of β-amyloid peptides (Aβ) and intracellular neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau (pTau) protein in the brain. Genetic and animal studies strongly indicate that Aβ, tau and neuroinflammation play important roles in the pathogenesis of AD. Several staging models showed that NFTs correlated well with the disease progression.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!