Here’s the text of an abstract I’ll be presenting at the European Molecular Biology Organization (EMBO) autophagy conference in Norway in May 2013:
Occasional periods of very low-protein, high-carbohydrate dietary intake may enhance lysosomal proteolysis in Alzheimer’s disease (AD) by increasing activity of transcription factor EB (TFEB) via inhibition of glycogen synthase kinase 3 (GSK3).
AD is characterized by 1) activation of neuronal autophagy with defective autolysosomal degradation, and 2) neuronal insulin resistance, characterized by increased amyloid-β (Aβ) production in autophagosomes and reduced neuronal internalization of extracellular Aβ oligomers.
Suitable AD therapies may therefore aim to reduce neuronal insulin resistance and increase activity of TFEB, a master gene regulator of lysosomal biogenesis. Upon cellular starvation and in response to inhibition of mammalian target of rapamycin (mTOR), TFEB translocates from the cytosol to the nucleus, whereupon it increases transcription of 291 genes, including many involved in autophagy. At least 20 of these genes participate in lysosomal biogenesis, acidification, and proteolysis.