Parkinson’s Disease
A Progressive Neurodegenerative Disorder
Parkinson’s disease (PD) is a progressive neurodegenerative disorder primarily characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta of the midbrain, leading to a marked reduction in striatal dopamine levels. This dopamine deficiency disrupts the normal functioning of basal ganglia circuits, resulting in the cardinal motor symptoms of PD: bradykinesia, resting tremor, rigidity, and postural instability.
Cellular Pathology: α-Synuclein and Mitophagy Failure
Pathologically, PD is marked by the presence of intracellular inclusions known as Lewy bodies, composed primarily of aggregated α-synuclein. Aggregated α-synuclein as well as other stress factors induce mitochondrial damage. A failure to clear damaged mitochondria via mitophagy results in accumulation of damaged mitochondria and eventually cell death.
Molecular Triggers and Clearance Mechanism
Figure 6. Neurotoxic amyloid oligomers, hyperphosphorylated tau aggregates and aggregated alpha-synuclein drive pathology in AD and PD. PINK1 activators promote clearance of hyperphosphorylated tau, aggregated alpha-synuclein and reduces amyloid oligomers resulting in neuroprotection and mitigation of pathology in PD and AD.
Therapeutic Innovation with Progenra
While the exact etiology remains multifactorial, involving genetic and environmental factors, ongoing research continues to investigate the molecular mechanisms underpinning PD and to develop disease-modifying therapies beyond current dopaminergic treatments. One such therapy being developed by Progenra includes PINK1 activators to promote mitophagy as well as clearance of toxic protein aggregates.
