The Transcellular Propagation and Intracellular Trafficking of α-Synuclein
Parkinson’s disease is the second most common neurodegenerative disorder, with only partial symptomatic therapy and no mechanism-based therapies. The accumulation and aggregation of α-synuclein is causatively linked to the sporadic form of the disease, which accounts for 95% of cases. The pathology...
| Main Authors: | , , |
|---|---|
| Format: | Journal article |
| Published: |
Cold Spring Harbor Laboratory Press
2016
|
| _version_ | 1797082470958497792 |
|---|---|
| author | Tofaris, GK Goedert, M Spillantini, MG |
| author_facet | Tofaris, GK Goedert, M Spillantini, MG |
| author_sort | Tofaris, GK |
| collection | OXFORD |
| description | Parkinson’s disease is the second most common neurodegenerative disorder, with only partial symptomatic therapy and no mechanism-based therapies. The accumulation and aggregation of α-synuclein is causatively linked to the sporadic form of the disease, which accounts for 95% of cases. The pathology is a result of a gain of toxic function of misfolded α-synuclein conformers, which can template the aggregation of soluble monomers and lead to cellular dysfunction, at least partly by interfering with membrane fusion events at synaptic terminals. Here, we discuss the transcellular propagation and intracellular trafficking of α-synuclein and posit that endosomal processing could be a point of convergence between these two routes. Understanding these events will clarify the therapeutic potential of enzymes that regulate protein trafficking and degradation in synucleinopathies. |
| first_indexed | 2024-03-07T01:28:35Z |
| format | Journal article |
| id | oxford-uuid:92ceb3a7-0e7f-4f8a-8832-0cce630b3a21 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T01:28:35Z |
| publishDate | 2016 |
| publisher | Cold Spring Harbor Laboratory Press |
| record_format | dspace |
| spelling | oxford-uuid:92ceb3a7-0e7f-4f8a-8832-0cce630b3a212022-03-26T23:28:08ZThe Transcellular Propagation and Intracellular Trafficking of α-SynucleinJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:92ceb3a7-0e7f-4f8a-8832-0cce630b3a21Symplectic Elements at OxfordCold Spring Harbor Laboratory Press2016Tofaris, GKGoedert, MSpillantini, MGParkinson’s disease is the second most common neurodegenerative disorder, with only partial symptomatic therapy and no mechanism-based therapies. The accumulation and aggregation of α-synuclein is causatively linked to the sporadic form of the disease, which accounts for 95% of cases. The pathology is a result of a gain of toxic function of misfolded α-synuclein conformers, which can template the aggregation of soluble monomers and lead to cellular dysfunction, at least partly by interfering with membrane fusion events at synaptic terminals. Here, we discuss the transcellular propagation and intracellular trafficking of α-synuclein and posit that endosomal processing could be a point of convergence between these two routes. Understanding these events will clarify the therapeutic potential of enzymes that regulate protein trafficking and degradation in synucleinopathies. |
| spellingShingle | Tofaris, GK Goedert, M Spillantini, MG The Transcellular Propagation and Intracellular Trafficking of α-Synuclein |
| title | The Transcellular Propagation and Intracellular Trafficking of α-Synuclein |
| title_full | The Transcellular Propagation and Intracellular Trafficking of α-Synuclein |
| title_fullStr | The Transcellular Propagation and Intracellular Trafficking of α-Synuclein |
| title_full_unstemmed | The Transcellular Propagation and Intracellular Trafficking of α-Synuclein |
| title_short | The Transcellular Propagation and Intracellular Trafficking of α-Synuclein |
| title_sort | transcellular propagation and intracellular trafficking of α synuclein |
| work_keys_str_mv | AT tofarisgk thetranscellularpropagationandintracellulartraffickingofasynuclein AT goedertm thetranscellularpropagationandintracellulartraffickingofasynuclein AT spillantinimg thetranscellularpropagationandintracellulartraffickingofasynuclein AT tofarisgk transcellularpropagationandintracellulartraffickingofasynuclein AT goedertm transcellularpropagationandintracellulartraffickingofasynuclein AT spillantinimg transcellularpropagationandintracellulartraffickingofasynuclein |