Fig. 2

Balance and imbalance of proteostasis implicated in PD pathogenesis Under physiological conditions, the modulation of protein biogenesis, chaperone capacity and protein degradation can counteract against deleterious factors and stress challenge-induced protein misfolding and proteostasis dysfunction (a). Under pathological conditions, such as PD-associated gene mutations, environmental toxin challenges and pathological aging, the protective capacities of the proteostasis mechanisms are impaired, whereas stress-induced protein misfolding, mitochondria impairment and oxidative stress are aggravated. This can lead to the imbalance of proteostasis and protein aggregation, contributing to neurodegeneration in PD (b)