Parkinson´s Disease (PD) is the second most common neurodegenerative disorder, af-fecting ~2-3% of the population over 65 years old. In addition to progressive degeneration of ni-grostriatal neurons, the histopathological feature of PD is the accumulation of misfolded α-synu-clein protein in abnormal cytoplasmatic inclusions, known as Lewy Bodies (LBs). Recently, Genome-Wide Association Studies (GWAS) have indicated a clear association of variants within several lysosomal genes with risk for PD. Newly evolving data have been shedding light on the relationship between lysosomal dysfunction and alpha-synuclein aggregation. Defects in lysosomal enzymes could lead to the insufficient clearance of neurotoxic protein materials, possibly leading to selective degeneration of dopaminergic neurons. Specific modulation of lysosomal pathways and their components could be considered a novel opportunity for therapeutic intervention for PD. The purpose of this review is to illustrate lysosomal biology and describe the role of lysosomal dysfunction in PD pathogenesis. Finally, the most promising novel therapeutic approaches designed to modulate lysosomal activity, as a potential disease-modifying treatment for PD will be highlighted.
Are Lysosomes Potential Therapeutic Targets for Parkinson’s Disease?
Blandini F.
2022-01-01
Abstract
Parkinson´s Disease (PD) is the second most common neurodegenerative disorder, af-fecting ~2-3% of the population over 65 years old. In addition to progressive degeneration of ni-grostriatal neurons, the histopathological feature of PD is the accumulation of misfolded α-synu-clein protein in abnormal cytoplasmatic inclusions, known as Lewy Bodies (LBs). Recently, Genome-Wide Association Studies (GWAS) have indicated a clear association of variants within several lysosomal genes with risk for PD. Newly evolving data have been shedding light on the relationship between lysosomal dysfunction and alpha-synuclein aggregation. Defects in lysosomal enzymes could lead to the insufficient clearance of neurotoxic protein materials, possibly leading to selective degeneration of dopaminergic neurons. Specific modulation of lysosomal pathways and their components could be considered a novel opportunity for therapeutic intervention for PD. The purpose of this review is to illustrate lysosomal biology and describe the role of lysosomal dysfunction in PD pathogenesis. Finally, the most promising novel therapeutic approaches designed to modulate lysosomal activity, as a potential disease-modifying treatment for PD will be highlighted.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
