Target Information
Target General Information | Top | |||||
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Target ID |
T03644
(Former ID: TTDI02186)
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Target Name |
Synuclein alpha (SNCA)
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Synonyms |
PARK1; Non-A4 component of amyloid precursor; Non-A beta component of AD amyloid; NACP; Alpha-synuclein
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Gene Name |
SNCA
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 3 Target-related Diseases | + | ||||
1 | Alzheimer disease [ICD-11: 8A20] | |||||
2 | Autonomic nervous system disorder [ICD-11: 8D87] | |||||
3 | Parkinsonism [ICD-11: 8A00] | |||||
Function |
Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release. Participates as a monomer in synaptic vesicle exocytosis by enhancing vesicle priming, fusion and dilation of exocytotic fusion pores. Mechanistically, acts by increasing local Ca(2+) release from microdomains which is essential for the enhancement of ATP-induced exocytosis. Acts also as a molecular chaperone in its multimeric membrane-bound state, assisting in the folding of synaptic fusion components called SNAREs (Soluble NSF Attachment Protein REceptors) at presynaptic plasma membrane in conjunction with cysteine string protein-alpha/DNAJC5. This chaperone activity is important to sustain normal SNARE-complex assembly during aging. Plays also a role in the regulation of the dopamine neurotransmission by associating with the dopamine transporter (DAT1) and thereby modulating its activity.
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BioChemical Class |
Synuclein
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UniProt ID | ||||||
Sequence |
MDVFMKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVATVAEKTK
EQVTNVGGAVVTGVTAVAQKTVEGAGSIAAATGFVKKDQLGKNEEGAPQEGILEDMPVDP DNEAYEMPSEEGYQDYEPEA Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
HIT2.0 ID | T58CAO |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 6 Clinical Trial Drugs | + | ||||
1 | BIIB054 | Drug Info | Phase 2 | Parkinson disease | [2] | |
2 | PRX002 | Drug Info | Phase 2 | Parkinson disease | [3] | |
3 | RG7935 | Drug Info | Phase 2 | Parkinson disease | [2] | |
4 | MEDI1341 | Drug Info | Phase 1 | Parkinson disease | [2] | |
5 | NPT200-11 | Drug Info | Phase 1 | Multiple system atrophy | [2] | |
6 | Posiphen R-phenserine | Drug Info | Phase 1 | Alzheimer disease | [4] | |
Mode of Action | [+] 2 Modes of Action | + | ||||
Inhibitor | [+] 4 Inhibitor drugs | + | ||||
1 | BIIB054 | Drug Info | [2] | |||
2 | PRX002 | Drug Info | [5] | |||
3 | MEDI1341 | Drug Info | [2] | |||
4 | NPT200-11 | Drug Info | [6] | |||
Modulator | [+] 1 Modulator drugs | + | ||||
1 | Posiphen R-phenserine | Drug Info | [4], [7] |
Chemical Structure based Activity Landscape of Target | Top |
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Target Poor or Non Binders | Top | |||||
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Target Poor or Non Binders |
Target Regulators | Top | |||||
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Target-regulating microRNAs | ||||||
Target-interacting Proteins |
Target Profiles in Patients | Top | |||||
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Target Expression Profile (TEP) |
Target Affiliated Biological Pathways | Top | |||||
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KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
1 | Alzheimer's disease | |||||
2 | Parkinson's disease | |||||
NetPath Pathway | [+] 2 NetPath Pathways | + | ||||
1 | Leptin Signaling Pathway | |||||
2 | RANKL Signaling Pathway | |||||
Panther Pathway | [+] 1 Panther Pathways | + | ||||
1 | Parkinson disease | |||||
PID Pathway | [+] 1 PID Pathways | + | ||||
1 | Alpha-synuclein signaling | |||||
Reactome | [+] 1 Reactome Pathways | + | ||||
1 | Amyloid formation | |||||
WikiPathways | [+] 4 WikiPathways | + | ||||
1 | Ectoderm Differentiation | |||||
2 | Parkinsons Disease Pathway | |||||
3 | Parkin-Ubiquitin Proteasomal System pathway | |||||
4 | Alzheimers Disease |
References | Top | |||||
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REF 1 | alpha-Synuclein in Parkinson's Disease. Cold Spring Harb Perspect Med. 2012 February; 2(2): a009399. | |||||
REF 2 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
REF 3 | ClinicalTrials.gov (NCT03100149) A Study to Evaluate the Efficacy of Prasinezumab (RO7046015/PRX002) in Participants With Early Parkinson's Disease (PASADENA). U.S. National Institutes of Health. | |||||
REF 4 | The Anticholinesterase Phenserine and Its Enantiomer Posiphen as 5 ntranslated-Region-Directed Translation Blockers of the Parkinson's Alpha Synuclein Expression. Parkinson's Disease Volume 2012 (2012), Article ID 142372, Page(13). | |||||
REF 5 | Safety and Tolerability of Multiple Ascending Doses of PRX002/RG7935, an Anti-alpha-Synuclein Monoclonal Antibody, in Patients With Parkinson Disease: A Randomized Clinical Trial. JAMA Neurol. 2018 Oct 1;75(10):1206-1214. | |||||
REF 6 | The small molecule alpha-synuclein misfolding inhibitor, NPT200-11, produces multiple benefits in an animal model of Parkinson's disease. Sci Rep. 2018 Nov 1;8(1):16165. | |||||
REF 7 | The Anticholinesterase Phenserine and Its Enantiomer Posiphen as 5 ntranslated-Region-Directed Translation Blockers of the Parkinson's Alpha Synuclein Expression. Parkinson's Disease Volume 2012 (2012), Article ID 142372, Page(13). |
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