A New Direction in Parkinson’s Treatment: Slowing Disease Progression by Targeting Alpha-synuclein

ანოტაცია

Introduction: Parkinson's disease is one of the most prevalent neurological disorders. Currently, dopamine replacement therapy is used to treat the disease's motor impairments. Moreover, levodopa does not slow the progression of the disorder, and its side effects are certain. Drugs designed to slow the condition's progression are therefore required, and when taken in conjunction with existing therapeutic approaches, these medications may offer advantages not achievable with single-drug treatments. This systematic review outlines a therapeutic approach that targets alpha-synuclein, a protein whose aggregation causes Lewy bodies and the degeneration of these dopaminergic neurons. This is accomplished by looking at previously published articles that have been compiled from various databases. Future research aims to slow the condition's progression by concentrating on the mechanism or cause—such as genes or Lewy bodies—that leads to neuronal degeneration. Methods: This quantitative data was gathered through secondary research on multiple articles that primarily addressed this article. We gathered the articles from databases like PubMed, MedLine, and PubMed Central. Keywords such as "Parkinson disorder," "treatment for Parkinson disorder," "medications for Parkinson disorder," and "medications for alpha-synuclein" were used to locate and gather the required articles. Following keyword research, 7011 PubMeD papers were ultimately found. These articles were filtered using the following criteria: they had to be written entirely in English, be based on case reports and clinical trials, only use human and animal models, and have been published within the last five years. Ideally, simple reviews and systematic reviews were excluded from the list. After this analysis, only 17 articles were chosen for additional research. Results: The 17 selected research papers were analyzed once more, and those that included therapy exclusively for alpha-synuclein— excluding all other targets—as well as those that exclusively addressed Parkinson's disease and those that were solely therapeutic in nature rather than diagnostic were given priority. Therapeutic options for this disorder that were undergoing clinical development were included in the five research papers that made the short list. Treatment with ambroxol—upregulation of GCase expression, which may directly contribute to the elimination of alpha-synuclein proteins. A tiny molecule known as Syn-Ribo TAC binds to the SNCA mRNA and breaks it down. Cinpanemab, a monoclonal antibody that preferentially binds to aggregated forms of extracellular alpha-synuclein, and prasinezumab are used in antibody therapy. Monomeric alpha-synuclein is modestly and gradually compacted by cyclized nordihydroguaiaretic acid, which stops it from clumping together to form amyloid-like fibrils. Conclusion: The main goals of the therapeutic strategies discussed here are to reduce alpha-synuclein levels, stop it from aggregating and becoming toxic, and treat aggregated alpha-synuclein with antibodies. Since the antibody treatment medications have failed in their clinical trials and are still undergoing clinical trials, more research is required to pinpoint this alpha-synuclein using more effective methods. Future studies should concentrate on genetic mutations in the genes linked to Parkinson's disease and the development of gene-targeted therapies, which may slow the disease's progression and provide better effects.