David PS
Member
Yet another benefit of aspirin (at least for mice). It decreased amyloid plaque load. Aspirin may not cure AD but reducing plaque be beneficial for AD and lysosomal storage disorders. Either way, the low cost of aspirin makes it accessible to many.
www.jneurosci.org
SIGNIFICANCE STATEMENT Developing drugs for the reduction of amyloid β containing senile plaques, one of the pathological hallmarks of Alzheimer's disease (AD), is an important area of research. Aspirin, one of the most widely used medications in the world, activates peroxisome proliferator-activated receptor alpha (PPARα) to upregulate transcription factor EB and increase lysosomal biogenesis in brain cells. Accordingly, low-dose aspirin decreases cerebral plaque load in a mouse model of Alzheimer's disease via PPARα. These results reveal a new mode of action of aspirin that may be beneficial for AD and lysosomal storage disorders.
Aspirin Induces Lysosomal Biogenesis and Attenuates Amyloid Plaque Pathology in a Mouse Model of Alzheimer's Disease via PPARα
Lysosomes play a central role in cellular homeostasis by regulating the cellular degradative machinery. Because aberrant lysosomal function has been associated with multiple lysosomal storage and neurodegenerative disorders, enhancement of lysosomal clearance has emerged as an attractive...
Abstract
Lysosomes play a central role in cellular homeostasis by regulating the cellular degradative machinery. Because aberrant lysosomal function has been associated with multiple lysosomal storage and neurodegenerative disorders, enhancement of lysosomal clearance has emerged as an attractive therapeutic strategy. Transcription factor EB (TFEB) is known as a master regulator of lysosomal biogenesis and, here, we reveal that aspirin, one of the most widely used medications in the world, upregulates TFEB and increases lysosomal biogenesis in brain cells. Interestingly, aspirin induced the activation of peroxisome proliferator-activated receptor alpha (PPARα) and stimulated the transcription of Tfeb via PPARα. Finally, oral administration of low-dose aspirin decreased amyloid plaque pathology in both male and female 5X familial Alzheimer's disease (5XFAD) mice in a PPARα-dependent fashion. This study reveals a new function of aspirin in stimulating lysosomal biogenesis via PPARα and suggests that low-dose aspirin may be used in lowering storage materials in Alzheimer's disease and lysosomal storage disorders.SIGNIFICANCE STATEMENT Developing drugs for the reduction of amyloid β containing senile plaques, one of the pathological hallmarks of Alzheimer's disease (AD), is an important area of research. Aspirin, one of the most widely used medications in the world, activates peroxisome proliferator-activated receptor alpha (PPARα) to upregulate transcription factor EB and increase lysosomal biogenesis in brain cells. Accordingly, low-dose aspirin decreases cerebral plaque load in a mouse model of Alzheimer's disease via PPARα. These results reveal a new mode of action of aspirin that may be beneficial for AD and lysosomal storage disorders.
