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α-Synuclein at the Presynaptic Axon Terminal as a Double-Edged Sword
| Content Provider | MDPI |
|---|---|
| Author | Tan, Li Yang Tang, Kwan Hou Lim, Lynette Yu You Ong, Jia Xin Park, Hyokeun Jung, Sangyong |
| Copyright Year | 2022 |
| Description | α-synuclein (α-syn) is a presynaptic, lipid-binding protein strongly associated with the neuropathology observed in Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and Alzheimer’s Disease (AD). In normal physiology, α-syn plays a pivotal role in facilitating endocytosis and exocytosis. Interestingly, mutations and modifications of precise α-syn domains interfere with α-syn oligomerization and nucleation that negatively affect presynaptic vesicular dynamics, protein expressions, and mitochondrial profiles. Furthermore, the integration of the α-syn oligomers into the presynaptic membrane results in pore formations, ion influx, and excitotoxicity. Targeted therapies against specific domains of α-syn, including the use of small organic molecules, monoclonal antibodies, and synthetic peptides, are being screened and developed. However, the prospect of an effective α-syn targeted therapy is still plagued by low permeability across the blood–brain barrier (BBB), and poor entry into the presynaptic axon terminals. The present review proposes a modification of current strategies, which includes the use of novel encapsulation technology, such as lipid nanoparticles, to bypass the BBB and deliver such agents into the brain. |
| Starting Page | 507 |
| e-ISSN | 2218273X |
| DOI | 10.3390/biom12040507 |
| Journal | Biomolecules |
| Issue Number | 4 |
| Volume Number | 12 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2022-03-27 |
| Access Restriction | Open |
| Subject Keyword | Biomolecules Neurosciences Α-synuclein Parkinson's Disease Lewy Bodies (lb) Dementia with Lewy Bodies Synucleinopathy Presynaptic Axon Terminal Α-synuclein Oligomerization Synaptic Vesicle Endocytosis Targeted Therapy |
| Content Type | Text |
| Resource Type | Article |
