Lysosomal Storage Diseases-Regulating Neurodegeneration

Area of Science:

• Cell Biology
• Biochemistry
• Genetics

Background:

• Lysosomal storage diseases (LSDs) are genetic disorders characterized by the accumulation of undegraded cellular material within lysosomes.
• The understanding of LSDs originated from the discovery of enzyme deficiencies, such as in Pompe disease in 1963.
• Autophagy, a cellular degradation and recycling process, is intricately linked with lysosomal function and can be impaired in LSDs.

Purpose of the Study:

• To review the biology of lysosomal storage diseases (LSDs).
• To summarize well-characterized LSDs and their affected pathways.
• To highlight the particular vulnerability of the nervous system to LSDs.

Main Methods:

• Literature review of established research on LSDs.
• Analysis of signaling pathways implicated in autophagy and lysosomal function.
• Compilation of data on the prevalence of nervous system involvement in LSDs.

Main Results:

• LSDs result from defective lysosomal degradation, leading to material accumulation.
• The nervous system (central and peripheral) is disproportionately affected, with two-thirds of LSDs impacting neural tissues.
• Autophagy is a key pathway perturbed in various LSDs.

Conclusions:

• Autophagy plays a critical role in cellular homeostasis and is frequently dysregulated in LSDs.
• The nervous system's susceptibility underscores the need for targeted research and therapies for neurological LSDs.
• Further understanding of LSDs and their molecular pathways is essential for therapeutic development.