Autophagy in Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is a devastating disease associated with accumulation of α-synuclein (α-Syn) within dopaminergic neurons, leading to neuronal death. PD is characterized by both motor and non-motor clinical symptoms. Several studies indicate that autophagy, an important intracellular degradation pathway, may be involved in different neurodegenerative diseases including PD. The autophagic process mediates the degradation of protein aggregates, damaged and unneeded proteins, and organelles, allowing their clearance, and thereby maintaining cell homeostasis. Impaired autophagy may cause the accumulation of abnormal proteins. Incomplete or impaired autophagy may explain the neurotoxic accumulation of protein aggregates in several neurodegenerative diseases including PD. Indeed, studies have suggested the contribution of impaired autophagy to α-Syn accumulation, the death of dopaminergic neurons, and neuroinflammation. In this review, we summarize the recent literature on the involvement of autophagy in PD pathogenesis.

Targets to Search for New Pharmacological Treatment in Idiopathic Parkinson’s Disease According to the Single-Neuron Degeneration Model

“…The discovery in 1960 that low dopamine levels in Parkinson’s disease are a product of the loss of dopaminergic neurons that contain neuromelanin has been one of the most important discoveries in understanding the molecular mechanisms of this disease. However, although several mechanisms related to the neurodegeneration of the nigrostriatal system have been identified, such as mitochondrial dysfunction, oxidative stress, dysfunction of both proteasomal and lysosomal protein degradation systems, endoplasmic reticulum stress, neuroinflammation, and the formation of neurotoxic oligomers of alpha-synuclein, it is not yet known what triggers these mechanisms [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ].…”

Neuroinflammation and Neurodegenerative Diseases: How Much Do We Still Not Know?

“…It has been demonstrated to be involved in neuroinflammation and ND, which are characterized by protein aggregation and exacerbated autophagy [72][73][74]. However, the mechanisms involved are not clear [75][76][77]. Despite this, some drugs, including cocaine [78] or other toxic substances of exogenous or endogenous nature and pathogens have been tested to evoke autophagic cell death in astrocytes and in consequent pathogenesis of neurodegeneration [79].…”

The role of autophagy in Parkinson’s disease: a gender difference overview

“…PD is one of the most common neurodegenerative diseases, characterized by an accumulation of α-synuclein (α-Syn) protein within dopaminergic neurons, carrying to neuronal death ( Sveinbjornsdottir, 2016 ). Autophagic processes, responsible for removing damaged proteins and managing cell balance, play a key role in understanding the pathogenesis of the disease ( Nechushtai et al, 2023 ). Recently, more studies have focused on gender disparities in the manifestation and progression of PD.…”