Targeting selective autophagy in CNS disorders by small-molecule compounds

Area of Science:

• Cell Biology
• Neuroscience
• Biochemistry

Background:

• Autophagy is the main cellular process for clearing waste.
• Selective autophagy, unlike bulk autophagy, is critical in central nervous system (CNS) disorder progression.
• Mitophagy (mitochondrial autophagy) is understood in brain disease, but other selective autophagy substrates also play roles.

Purpose of the Study:

• To highlight the importance of selective autophagy in CNS disorders.
• To review chemical compounds that modulate selective autophagy in CNS disorders.
• To discuss the mechanisms underlying selective autophagy regulation.

Main Methods:

• Literature review of selective autophagy in CNS disorders.
• Analysis of molecular mechanisms (ubiquitin-dependent and -independent pathways).
• Identification of small-molecule compounds and natural products regulating selective autophagy.

Main Results:

• Selective autophagy of various substrates (mitochondria, protein aggregates, ER) impacts CNS pathology.
• Both ubiquitin-dependent and -independent pathways govern selective autophagy.
• Small-molecule compounds, particularly natural products, can modulate selective autophagy.

Conclusions:

• Selective autophagy plays a critical role in the pathogenesis of CNS disorders.
• Targeting selective autophagy pathways with chemical compounds presents a promising therapeutic strategy.
• Further research into these compounds will advance understanding and treatment of brain disorders.