Review Volume 12, Issue 21 pp 22313—22334

α-Synuclein in traumatic and vascular diseases of the central nervous system

Hong Zeng1, , Nan Liu1, , Xiao-Xie Liu1, , Yan-Yan Yang1, , Mou-Wang Zhou1, ,

  • 1 Department of Rehabilitation Medicine, Peking University Third Hospital, Beijing 100191, China

Received: January 30, 2020       Accepted: June 29, 2020       Published: November 7, 2020
How to Cite

Copyright: © 2020 Zeng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


α-Synuclein (α-Syn) is a small, soluble, disordered protein that is widely expressed in the nervous system. Although its physiological functions are not yet fully understood, it is mainly involved in synaptic vesicle transport, neurotransmitter synthesis and release, cell membrane homeostasis, lipid synthesis, mitochondrial and lysosomal activities, and heavy metal removal. The complex and inconsistent pathological manifestations of α-Syn are attributed to its structural instability, mutational complexity, misfolding, and diverse posttranslational modifications. These effects trigger mitochondrial dysfunction, oxidative stress, and neuroinflammatory responses, resulting in neuronal death and neurodegeneration. Several recent studies have discovered the pathogenic roles of α-Syn in traumatic and vascular central nervous system diseases, such as traumatic spinal cord injury, brain injury, and stroke, and in aggravating the processes of neurodegeneration. This review aims to highlight the structural and pathophysiological changes in α-Syn and its mechanism of action in traumatic and vascular diseases of the central nervous system.


α-Syn: α-Synuclein; IDP: inherently disordered protein; PD: Parkinson disease; NTD: N-terminal domain; CTD: C-terminal domain; SNARE: soluble NSF attachment protein receptor; CSF: cerebrospinal fluid; EVs: extracellular vesicles; DA: dopamine; CSPα: cysteine choline protein α; ER: endoplasmic reticulum; VDACs: voltage-dependent anion channels; SN: substantia nigra; HDL: high-density lipoprotein; ROS: reactive oxygen species; RNS: reactive nitrogen species; PTM: Post-translational modification; Ser-129: Serine-129; PLK2: Polo-like kinase 2; PP2A: Protein phosphatase 2; SDS: sodium lauryl sulfate; UPS: ubiquitin proteasome system; ALP: autophagy lysosomal pathway; AGEs: advanced glycosylation end products; LB: Lewy bodies; AD: autonomic dysfunction; GCase: glucocerebrosidase; CNS: central nervous system; LC3B: light chain 3B; FcγR: Fc-γ receptors; TLR: Toll-like receptor; TNF-α: tumor necrosis factor-α; IL: interleukin; MCP-1: monocyte chemotactic protein-1; IFN: interferon; iNOS: inducible nitric oxide synthase; Arg1: arginase 1; MSCs: mesenchymal stem cells; GABA: γ-aminobutyrate; VGT-1: vesicle glutamate transporter-1; SCI: spinal cord injury; HIF-1α: hypoxiain-duciblefactors-1α; CNTF: ciliary neurotrophic factor; Chrm2: muscarinic cholinergic receptor subtype 2; Chrnb2: nicotinic cholinergic receptor β2; TBI: Traumatic brain injury; CTE: chronic traumatic encephalopathy; BBB: Blood-brain barrier; TH: tyrosine hydroxylase; SNpc: dense substantia nigra; Aβ: amyloid β; MCAO: middle cerebral artery occlusion; PPARγ: peroxisome proliferator-activated receptor γ; KO: knockout; Drp13): dynamin-related protein 1.