Novel approaches targeting α-Synuclein for Parkinson's Disease: Current progress and future directions for the disease-modifying therapies
Parkinson's Disease (PD) is a common and debilitating neurodegenerative disorder affecting millions worldwide. The hallmark pathological feature of PD is the accumulation and aggregation of α-Synuclein (α-Syn), a protein involved in synaptic function and neuronal survival. The formation of α-Sy...
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Elsevier
2024-12-01
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| Series: | Brain Disorders |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666459324000489 |
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| author | David Baggett Alex Olson Mayur S. Parmar |
| author_facet | David Baggett Alex Olson Mayur S. Parmar |
| author_sort | David Baggett |
| collection | DOAJ |
| description | Parkinson's Disease (PD) is a common and debilitating neurodegenerative disorder affecting millions worldwide. The hallmark pathological feature of PD is the accumulation and aggregation of α-Synuclein (α-Syn), a protein involved in synaptic function and neuronal survival. The formation of α-Syn aggregates, also known as Lewy bodies and Lewy neurites, leads to neuronal dysfunction and death, resulting in PD's characteristic motor and non-motor symptoms. Current treatments for PD are mainly symptomatic and do not address the underlying cause of the disease. Therefore, there is an urgent need for disease-modifying therapies that can prevent, slow, or reverse the progression of PD by targeting α-Syn aggregation. In this review, we summarize the current status of pharmacological interventions that aim to reduce α-Syn levels in PD and other Synucleinopathies by various mechanisms, such as inhibiting α-Syn aggregation, enhancing α-Syn clearance, modulating α-Syn-related enzymes, or blocking α-Syn transmission. We focus on agents that have reached phase 1 or 2 clinical trials and provide an overview of their preclinical and clinical data and their safety and efficacy profiles. While fewer candidates have shown positive results in clinical trials, they are awaiting further evaluation in larger and longer-term studies. None of the placebo-controlled, blind trials, except Prasinezumab, have demonstrated efficacy. These novel disease-modifying therapy approaches can potentially change the landscape of PD treatment and improve the quality of life for PD patients. |
| format | Article |
| id | doaj-art-7f76d9b055074150b3fbd7bb04a978e4 |
| institution | Kabale University |
| issn | 2666-4593 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Disorders |
| spelling | doaj-art-7f76d9b055074150b3fbd7bb04a978e42024-12-04T05:13:56ZengElsevierBrain Disorders2666-45932024-12-0116100163Novel approaches targeting α-Synuclein for Parkinson's Disease: Current progress and future directions for the disease-modifying therapiesDavid Baggett0Alex Olson1Mayur S. Parmar2Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Clearwater Campus, Florida, USADr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Clearwater Campus, Florida, USACorresponding author.; Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Clearwater Campus, Florida, USAParkinson's Disease (PD) is a common and debilitating neurodegenerative disorder affecting millions worldwide. The hallmark pathological feature of PD is the accumulation and aggregation of α-Synuclein (α-Syn), a protein involved in synaptic function and neuronal survival. The formation of α-Syn aggregates, also known as Lewy bodies and Lewy neurites, leads to neuronal dysfunction and death, resulting in PD's characteristic motor and non-motor symptoms. Current treatments for PD are mainly symptomatic and do not address the underlying cause of the disease. Therefore, there is an urgent need for disease-modifying therapies that can prevent, slow, or reverse the progression of PD by targeting α-Syn aggregation. In this review, we summarize the current status of pharmacological interventions that aim to reduce α-Syn levels in PD and other Synucleinopathies by various mechanisms, such as inhibiting α-Syn aggregation, enhancing α-Syn clearance, modulating α-Syn-related enzymes, or blocking α-Syn transmission. We focus on agents that have reached phase 1 or 2 clinical trials and provide an overview of their preclinical and clinical data and their safety and efficacy profiles. While fewer candidates have shown positive results in clinical trials, they are awaiting further evaluation in larger and longer-term studies. None of the placebo-controlled, blind trials, except Prasinezumab, have demonstrated efficacy. These novel disease-modifying therapy approaches can potentially change the landscape of PD treatment and improve the quality of life for PD patients.http://www.sciencedirect.com/science/article/pii/S2666459324000489Parkinson's diseaseSynucleinopathyAlpha-synucleinLewy bodyTherapeuticsGBA |
| spellingShingle | David Baggett Alex Olson Mayur S. Parmar Novel approaches targeting α-Synuclein for Parkinson's Disease: Current progress and future directions for the disease-modifying therapies Brain Disorders Parkinson's disease Synucleinopathy Alpha-synuclein Lewy body Therapeutics GBA |
| title | Novel approaches targeting α-Synuclein for Parkinson's Disease: Current progress and future directions for the disease-modifying therapies |
| title_full | Novel approaches targeting α-Synuclein for Parkinson's Disease: Current progress and future directions for the disease-modifying therapies |
| title_fullStr | Novel approaches targeting α-Synuclein for Parkinson's Disease: Current progress and future directions for the disease-modifying therapies |
| title_full_unstemmed | Novel approaches targeting α-Synuclein for Parkinson's Disease: Current progress and future directions for the disease-modifying therapies |
| title_short | Novel approaches targeting α-Synuclein for Parkinson's Disease: Current progress and future directions for the disease-modifying therapies |
| title_sort | novel approaches targeting α synuclein for parkinson s disease current progress and future directions for the disease modifying therapies |
| topic | Parkinson's disease Synucleinopathy Alpha-synuclein Lewy body Therapeutics GBA |
| url | http://www.sciencedirect.com/science/article/pii/S2666459324000489 |
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