Title : Autophagy induction in neurons and glial cells of aged db db mice with neurodegenenation development

According to investigations by Nixon and Rubinsztein (2024) autophagy is a lysosome-based degradative process used to recycle obsolete cellular components and to eliminate damaged organelles as well as aggregate-prone proteins. The postmitotic nature and extremely polarized morphologies make neurons particularly vulnerable to disruptions caused by autophagy-lysosomal defects, especially as the brain in ages. Autophagy induction is a prospective approach to the treatment of neurodegeneration. Recently, trehalose attracted a special attention (Pupyshev et al., 2025) for treatment of neurodegeneration. It is an autophagy inducer with negligible adverse effects and is approved to use in humans according to FDA requirements. It is glucose disaccharide with a flexible alfa-1-1-glucosidic bond with unique properties to induce mTOR—independent autophagy. Type 2 diabetes is associated with the formation of the signs of Alzheimer’s disease (AD). We studied possible correction of neurodegeneration in db/db mice (male and female), a model of diabetes and obesity with neurodegeneration that develop sign of AD with age. Earlier we have shown positive effect of trehalose (2% solution drinking during 30 days) treatment in young (1-month) db/db mice (Korolenko et al., 2025). It was not clear trehalose effects in older (5-month) db/db mice. We have shown, that in aged db/db mice (male and female) trehalose did not induce a significant decrease of the body mass or blood glucose levels, but it decreased the expression of insulin receptor gene Insr. There was increase in lipofuscin levels in cortical neurons and glial cells (in electron microscopic study of neurons and glial cells of db/db mice), while trehalose drinking for 30 days did not attenuate the accumulation of the marker. Thus, a differentials effect of trehalose was obtained for old 5-months old db/db mice compared to yong db/db mice (in the both sexes). Possibly, the therapeutic effects of trehalose in db/db mice decreases with age and became ineffective in 5-months of age.

Dr. Tatiana Korolenko is cellular biochemist specializing in neurodegenerative diseases researches, their experimental models and outbreak response. She holds a PhD in Biochemistry from Novosibirsk Medical University. Dr. Korolenko has worked with Lysosomal Storage Diseases (experimental models) and has published extensively on reproduction of lysosomal storage syndromes in the experiment (hepatocytes, macrophages, neurons) and their prevention. She is currently the Professor of the Neurodegenerative Diseases study (Alzheimer disease) Program at the Scientific Research Institute of Neurosciences and Medicine, Novosibirsk, Russia.