Advancing Parkinson's Disease Research: Targeting Pathogenic Mechanisms with Emerging Therapies

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor symptoms such as bradykinesia, rigidity, and tremors, alongside non-motor impairments including cognitive decline and autonomic dysfunction.The disease arises from dopaminergic neuronal loss in the substantia nigra and the pathological aggregation of α-synuclein.Its multifactorial etiology involves genetic mutations, mitochondrial dysfunction, oxidative stress, neuroinflammation, and systemic factors such as gut-brain axis dysregulation.Current therapies, including levodopa and deep brain stimulation, provide symptomatic relief but fail to halt disease progression.Recent advancements in molecular biology and neuroimaging have improved understanding and diagnostics, paving the way for disease-modifying therapies.Gene therapies, immunotherapies, molecular chaperones, and GLP-1 receptor agonists offer promising approaches to addressing pathogenic mechanisms such as α-synuclein aggregation, lysosomal dysfunction, and neuroinflammation.Additionally, cellreplacement therapies and neuroprotective natural compounds provide avenues for restoring neuronal function and mitigating progression.This review highlights the pathophysiology, diagnostic advancements, and emerging therapeutic strategies in PD, emphasizing their potential to transform patient care.Recently by finding new molecules and targets, In silico technologies are transforming the drug discovery process for Parkinson's disease (PD).These results provide a basis for developing synthetic and natural molecules as novel, multi-target PD therapies.