Parkinson's Disease: Molecular Mechanisms and Treatment Strategies.

Parkinson’s disease (PD) is the second most common neurodegenerative disorder in the elderly, clinically manifested by bradykinesia, resting tremor, postural instability, and hypermyotonia. Key pathological mechanisms implicated in PD onset include neuroinflammation, autophagy impairment, alpha-synuclein aggregation, and mitochondrial dysfunction. However, the precise molecular pathways underlying these processes remain to be fully elucidated. Currently, dopamine replacement therapy using levodopa/carbidopa is established as the gold standard of treatment for PD. No drug has been proven to slow disease progression. Recent findings highlight the pivotal role of the high-mobility group box 1 (HMGB1)/ receptor for advanced glycation end products (RAGE) axis in PD pathogenesis through its involvement in neuroinflammation, autophagy modulation, apoptosis regulation, and gene transcription. Additionally, the AMP-activated protein kinase (AMPK)/ silent information regulator 1 (SIRT1)/ peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) signaling axis has emerged as a crucial regulator of mitochondrial biogenesis and cellular energy homeostasis. Both HMGB1/RAGE and AMPK/SIRT1/PGC-1α pathways are gaining attention as promising therapeutic targets for developing interventions that could modify disease’s course and slow the progression of PD.