VPS35 and the mitochondria: Connecting the dots in Parkinson's disease pathophysiology
Mutations in VPS35 (PARK17), a key molecule in the retromer complex, are a rare cause of autosomal dominant Parkinson's disease (PD), the second most common neurodegenerative disorder. VPS35 exerts crucial functions within the cell in terms of regulating endosomal trafficking. However new data...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-11-01
|
| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996120303314 |
| _version_ | 1818673477169709056 |
|---|---|
| author | Gianni Cutillo David K. Simon Simona Eleuteri |
| author_facet | Gianni Cutillo David K. Simon Simona Eleuteri |
| author_sort | Gianni Cutillo |
| collection | DOAJ |
| description | Mutations in VPS35 (PARK17), a key molecule in the retromer complex, are a rare cause of autosomal dominant Parkinson's disease (PD), the second most common neurodegenerative disorder. VPS35 exerts crucial functions within the cell in terms of regulating endosomal trafficking. However new data suggest its relevance also in the regulation of mitochondrial dynamics and homeostasis. Herein, we review the crosstalk between VPS35 and the mitochondria, highlighting the potential relevance to PD pathogenesis. VPS35 is not only a critical player in pathways connected to α-synuclein accumulation and clearance, but also plays a key role in ensuring mitochondrial stability and function. The genetic links of VPS35 to PD and the involvement of VPS35 in different PD related pathological mechanisms highlight the potential for targeting VPS35 as a neuroprotective strategy for PD. |
| first_indexed | 2024-12-17T07:56:25Z |
| format | Article |
| id | doaj.art-47f8dc7c98804868875c6690717fb099 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T07:56:25Z |
| publishDate | 2020-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-47f8dc7c98804868875c6690717fb0992022-12-21T21:57:40ZengElsevierNeurobiology of Disease1095-953X2020-11-01145105056VPS35 and the mitochondria: Connecting the dots in Parkinson's disease pathophysiologyGianni Cutillo0David K. Simon1Simona Eleuteri2Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, MA 02215, USABeth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, MA 02215, USACorresponding author.; Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, MA 02215, USAMutations in VPS35 (PARK17), a key molecule in the retromer complex, are a rare cause of autosomal dominant Parkinson's disease (PD), the second most common neurodegenerative disorder. VPS35 exerts crucial functions within the cell in terms of regulating endosomal trafficking. However new data suggest its relevance also in the regulation of mitochondrial dynamics and homeostasis. Herein, we review the crosstalk between VPS35 and the mitochondria, highlighting the potential relevance to PD pathogenesis. VPS35 is not only a critical player in pathways connected to α-synuclein accumulation and clearance, but also plays a key role in ensuring mitochondrial stability and function. The genetic links of VPS35 to PD and the involvement of VPS35 in different PD related pathological mechanisms highlight the potential for targeting VPS35 as a neuroprotective strategy for PD.http://www.sciencedirect.com/science/article/pii/S0969996120303314VPS35Endosomal traffickingParkinson's diseaseMitochondrial dynamicNeuroprotectionTherapeutic approach |
| spellingShingle | Gianni Cutillo David K. Simon Simona Eleuteri VPS35 and the mitochondria: Connecting the dots in Parkinson's disease pathophysiology Neurobiology of Disease VPS35 Endosomal trafficking Parkinson's disease Mitochondrial dynamic Neuroprotection Therapeutic approach |
| title | VPS35 and the mitochondria: Connecting the dots in Parkinson's disease pathophysiology |
| title_full | VPS35 and the mitochondria: Connecting the dots in Parkinson's disease pathophysiology |
| title_fullStr | VPS35 and the mitochondria: Connecting the dots in Parkinson's disease pathophysiology |
| title_full_unstemmed | VPS35 and the mitochondria: Connecting the dots in Parkinson's disease pathophysiology |
| title_short | VPS35 and the mitochondria: Connecting the dots in Parkinson's disease pathophysiology |
| title_sort | vps35 and the mitochondria connecting the dots in parkinson s disease pathophysiology |
| topic | VPS35 Endosomal trafficking Parkinson's disease Mitochondrial dynamic Neuroprotection Therapeutic approach |
| url | http://www.sciencedirect.com/science/article/pii/S0969996120303314 |
| work_keys_str_mv | AT giannicutillo vps35andthemitochondriaconnectingthedotsinparkinsonsdiseasepathophysiology AT davidksimon vps35andthemitochondriaconnectingthedotsinparkinsonsdiseasepathophysiology AT simonaeleuteri vps35andthemitochondriaconnectingthedotsinparkinsonsdiseasepathophysiology |