A Critical Analysis of Quercetin as the Attractive Target for the Treatment of Parkinson's Disease

Parkinson's Disease (PD) is a multifaceted disorder with various factors suggested to play a synergistic pathophysiological role, such as oxidative stress, autophagy, pro-inflammatory events, and neurotransmitter abnormalities. While it is crucial to discover new treatments in addition to preventing PD, recent studies have focused on determining whether nutraceuticals will exert neuroprotective actions and pharmacological functions in PD. Quercetin, a flavonol-type flavonoid, is found in many fruits and vegetables and is recognised as a complementary therapy for PD. The neuroprotective effect of quercetin is directly associated with its antioxidant activity, in addition to stimulating cellular defence against oxidative stress. Other related mechanisms are activating Sirtuins (SIRT1) and inducing autophagy, in addition to induction of Nrf2-ARE and Paraoxonase 2 (PON2). Quercetin, whose neuroprotective activity has been demonstrated in many studies, unfortunately, has a disadvantage because of its poor water solubility, chemical instability, and low oral bioavailability. It has been reported that the disadvantages of quercetin have been eliminated with nanocarriers loaded with quercetin. The role of nanotechnology and nanodelivery systems in reducing oxidative stress during PD provides an indisputable advantage. Accordingly, the present review aims to shed light on quercetin's beneficial effects and underlying mechanisms in neuroprotection. In addition, the contribution of nanodelivery systems to the neuroprotective effect of quercetin is also discussed.