Title:Are Lysosomes Potential Therapeutic Targets for Parkinson’s Disease?
Volume: 21
Issue: 8
Author(s): Alessandro Petese, Valentina Cesaroni, Silvia Cerri and Fabio Blandini*
Affiliation:
- Cellular and Molecular Neurobiology Unit, IRCCS Mondino Foundation, Pavia, Italy
- Department of Brain and Behavioural
Sciences, University of Pavia, Pavia, Italy
Keywords:
Parkinson´s disease, PD GWAS loci, lysosomal pathways, alpha-synuclein, therapeutic approaches, LBs.
Abstract: Parkinson´s Disease (PD) is the second most common neurodegenerative disorder, affecting
~2-3% of the population over 65 years old. In addition to progressive degeneration of nigrostriatal
neurons, the histopathological feature of PD is the accumulation of misfolded α-synuclein
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.
