Abstract

MULTIFACTORIAL NEURODEGENERATION IN PARKINSON’S DISEASE: DECODING MOLECULAR PATHOLOGY, MODEL SYSTEMS, AND HERBAL THERAPEUTICS

Akshata Pattar and Prakash R. Biradar*

Abstract

Background: Parkinson's disease (PD) is a progressive neurodegenerative illness characterized by both motor and non-motor symptoms. It is caused by a combination of environmental and genetic variables, oxidative stress, mitochondrial dysfunction, alpha-synuclein aggregation, dopaminergic neuron loss, poor proteostasis, and neurons. Objective: This study aims to give a comprehensive overview of the molecular and cellular mechanisms that underlie Parkinson's disease, talk about the important hereditary and environmental factors that play a role, and highlight new multi-targeted therapy approaches that try to change the condition. Methods: The contributions of mitochondrial failure, oxidative stress, alpha-synuclein aggregation, neuroinflammation, defective autophagy-lysosomal and ubiquitinproteasome pathways, and changes in the gut-brain axis in Parkinson's disease pathogenesis were examined in a critical review of recent research. Research on new treatments that target these processes was also assessed. Results: Parkinson's disease is caused by a combination of environmental pollutants, mitochondrial malfunction, oxidative stress, proteostasis failure, neuroinflammation, gut microbiome alterations, and genetic abnormalities (SNCA, LRRK2, PINK1, GBA). Although dopaminergic treatments help with symptoms, they cannot stop neurodegeneration. Multi-targeted approaches are being developed to alter the course of disease, such as anti-inflammatory drugs and antioxidants derived from plants. Conclusion: Multiple pathogenic pathways must be targeted by integrative therapy due to the intricacy of Parkinson's disease. Novel approaches to disease-modifying treatments are presented by developments in experimental models and molecular research. Personalized, multimodal techniques must be the focus of future efforts in order to effectively control and change the course of disease.

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