Affiliations: [a] Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA
| [b] Division of Research and Development, Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA
Correspondence:
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Correspondence to: Kalipada Pahan, PhD, Department of Neurological Sciences, Rush University Medical Center, 1735 West Harrison St, Suite 310, Chicago, IL 60612, USA. Tel.:+1 312 563 3592; Fax: 312 563 3571; E-mail: Kalipada_Pahan@rush.edu.
Abstract: Mounting evidence has identified that impaired amyloid-β (Aβ) clearance might contribute to Alzheimer’s disease (AD) pathology. The lysosome-autophagy network plays an important role in protein homeostasis and cell health by removing abnormal protein aggregates via intracellular degradation. Therefore, stimulation of cellular degradative machinery for efficient removal of Aβ has emerged as a growing field in AD research. However, mechanisms controlling such pathways and drugs to promote such mechanisms are poorly understood. Aspirin is a widely used drug throughout the world and recent studies have identified a new function of this drug. At low doses, aspirin stimulates lysosomal biogenesis and autophagy to clear amyloid plaques in an animal model of AD. This review delineates such functions of aspirin and analyzes underlying mechanisms that involve peroxisome proliferator-activated receptor alpha (PPARα)-mediated transcription of transcription factor EB (TFEB), the master regulator of lysosomal biogenesis.
