Alpha-Synuclein and LRRK2 in Synaptic Autophagy: Linking Early Dysfunction to Late-Stage Pathology in Parkinson’s Disease
The lack of effective disease-modifying strategies is the major unmet clinical need in Parkinson’s disease. Several experimental approaches have attempted to validate cellular targets and processes. Of these, autophagy has received considerable attention in the last 20 years due to its involvement i...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-04-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/5/1115 |
| _version_ | 1797569224157167616 |
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| author | Giulia Lamonaca Mattia Volta |
| author_facet | Giulia Lamonaca Mattia Volta |
| author_sort | Giulia Lamonaca |
| collection | DOAJ |
| description | The lack of effective disease-modifying strategies is the major unmet clinical need in Parkinson’s disease. Several experimental approaches have attempted to validate cellular targets and processes. Of these, autophagy has received considerable attention in the last 20 years due to its involvement in the clearance of pathologic protein aggregates and maintenance of neuronal homeostasis. However, this strategy mainly addresses a very late stage of the disease, when neuropathology and neurodegeneration have likely “tipped over the edge” and disease modification is extremely difficult. Very recently, autophagy has been demonstrated to modulate synaptic activity, a process distinct from its catabolic function. Abnormalities in synaptic transmission are an early event in neurodegeneration with Leucine-Rich Repeat Kinase 2 (LRRK2) and alpha-synuclein strongly implicated. In this review, we analyzed these processes separately and then discussed the unification of these biomolecular fields with the aim of reconstructing a potential “molecular timeline” of disease onset and progression. We postulate that the elucidation of these pathogenic mechanisms will form a critical basis for the design of novel, effective disease-modifying therapies that could be applied early in the disease process. |
| first_indexed | 2024-03-10T20:07:50Z |
| format | Article |
| id | doaj.art-c600dd52f26242208689b1704e280c6d |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T20:07:50Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-c600dd52f26242208689b1704e280c6d2023-11-19T23:08:53ZengMDPI AGCells2073-44092020-04-0195111510.3390/cells9051115Alpha-Synuclein and LRRK2 in Synaptic Autophagy: Linking Early Dysfunction to Late-Stage Pathology in Parkinson’s DiseaseGiulia Lamonaca0Mattia Volta1Institute for Biomedicine, Eurac Research-Affiliated Institute of the University of Lübeck, 39100 Bolzano, ItalyInstitute for Biomedicine, Eurac Research-Affiliated Institute of the University of Lübeck, 39100 Bolzano, ItalyThe lack of effective disease-modifying strategies is the major unmet clinical need in Parkinson’s disease. Several experimental approaches have attempted to validate cellular targets and processes. Of these, autophagy has received considerable attention in the last 20 years due to its involvement in the clearance of pathologic protein aggregates and maintenance of neuronal homeostasis. However, this strategy mainly addresses a very late stage of the disease, when neuropathology and neurodegeneration have likely “tipped over the edge” and disease modification is extremely difficult. Very recently, autophagy has been demonstrated to modulate synaptic activity, a process distinct from its catabolic function. Abnormalities in synaptic transmission are an early event in neurodegeneration with Leucine-Rich Repeat Kinase 2 (LRRK2) and alpha-synuclein strongly implicated. In this review, we analyzed these processes separately and then discussed the unification of these biomolecular fields with the aim of reconstructing a potential “molecular timeline” of disease onset and progression. We postulate that the elucidation of these pathogenic mechanisms will form a critical basis for the design of novel, effective disease-modifying therapies that could be applied early in the disease process.https://www.mdpi.com/2073-4409/9/5/1115LRRK2autophagyParkinson’s diseasealpha-synucleinsynaptic transmissionneuropathology |
| spellingShingle | Giulia Lamonaca Mattia Volta Alpha-Synuclein and LRRK2 in Synaptic Autophagy: Linking Early Dysfunction to Late-Stage Pathology in Parkinson’s Disease Cells LRRK2 autophagy Parkinson’s disease alpha-synuclein synaptic transmission neuropathology |
| title | Alpha-Synuclein and LRRK2 in Synaptic Autophagy: Linking Early Dysfunction to Late-Stage Pathology in Parkinson’s Disease |
| title_full | Alpha-Synuclein and LRRK2 in Synaptic Autophagy: Linking Early Dysfunction to Late-Stage Pathology in Parkinson’s Disease |
| title_fullStr | Alpha-Synuclein and LRRK2 in Synaptic Autophagy: Linking Early Dysfunction to Late-Stage Pathology in Parkinson’s Disease |
| title_full_unstemmed | Alpha-Synuclein and LRRK2 in Synaptic Autophagy: Linking Early Dysfunction to Late-Stage Pathology in Parkinson’s Disease |
| title_short | Alpha-Synuclein and LRRK2 in Synaptic Autophagy: Linking Early Dysfunction to Late-Stage Pathology in Parkinson’s Disease |
| title_sort | alpha synuclein and lrrk2 in synaptic autophagy linking early dysfunction to late stage pathology in parkinson s disease |
| topic | LRRK2 autophagy Parkinson’s disease alpha-synuclein synaptic transmission neuropathology |
| url | https://www.mdpi.com/2073-4409/9/5/1115 |
| work_keys_str_mv | AT giulialamonaca alphasynucleinandlrrk2insynapticautophagylinkingearlydysfunctiontolatestagepathologyinparkinsonsdisease AT mattiavolta alphasynucleinandlrrk2insynapticautophagylinkingearlydysfunctiontolatestagepathologyinparkinsonsdisease |