Author, as appears in the article.: Folch J, Ettcheto M, Busquets O, Sánchez-López E, Castro-Torres RD, Verdaguer E, Manzine PR, Poor SR, García ML, Olloquequi J, Beas-Zarate C, Auladell C, Camins A.

Department: Bioquímica i Biotecnologia

URV's Author/s: Folch Lopez, Jaume

Keywords: Type 2 diabetes Tau Neurodegeneration Insulin resistance Insulin receptor Cognition Amyloid Alzheimer’s tau insulin resistance insulin receptor cognition amyloid alzheimer’s

Abstract: Alzheimer's disease (AD) is progressive neurodegenerative disorder characterized by brain accumulation of the amyloid β peptide (Aβ), which form senile plaques, neurofibrillary tangles (NFT) and, eventually, neurodegeneration and cognitive impairment. Interestingly, epidemiological studies have described a relationship between type 2 diabetes mellitus (T2DM) and this pathology, being one of the risk factors for the development of AD pathogenesis. Information as it is, it would point out that, impairment in insulin signalling and glucose metabolism, in central as well as peripheral systems, would be one of the reasons for the cognitive decline. Brain insulin resistance, also known as Type 3 diabetes, leads to the increase of Aβ production and TAU phosphorylation, mitochondrial dysfunction, oxidative stress, protein misfolding, and cognitive impairment, which are all hallmarks of AD. Moreover, given the complexity of interlocking mechanisms found in late onset AD (LOAD) pathogenesis, more data is being obtained. Recent evidence showed that Aβ42 generated in the brain would impact negatively on the hypothalamus, accelerating the 'peripheral' symptomatology of AD. In this situation, Aβ42 production would induce hypothalamic dysfunction that would favour peripheral hyperglycaemia due to down regulation of the liver insulin receptor. The objective of this review is to discuss the existing evidence supporting the concept that brain insulin resistance and altered glucose metabolism play an important role in pathogenesis of LOAD. Furthermore, we discuss AD treatment approaches targeting insulin signalling using anti-diabetic drugs and mTOR inhibitors.

Thematic Areas: Saúde coletiva Química Pharmacology & pharmacy Pharmaceutical science Molecular medicine Medicina ii Interdisciplinar Farmacia Drug discovery Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Chemistry, medicinal Biotecnología Biodiversidade

licence for use: https://creativecommons.org/licenses/by/3.0/es/

ISSN: 14248247

Author's mail: jaume.folch@urv.cat

Author identifier: 0000-0002-5051-8858

Record's date: 2023-02-18

Papper version: info:eu-repo/semantics/publishedVersion

Link to the original source: https://www.mdpi.com/1424-8247/11/1/11

Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/

Papper original source: Pharmaceuticals. 11 (1):

APA: Folch J, Ettcheto M, Busquets O, Sánchez-López E, Castro-Torres RD, Verdaguer E, Manzine PR, Poor SR, García ML, Olloquequi J, Beas-Zarate C, Auladell (2018). The Implication of the Brain Insulin Receptor in Late Onset Alzheimer's Disease Dementia.. Pharmaceuticals, 11(1), -. DOI: 10.3390/ph11010011

Article's DOI: 10.3390/ph11010011

Entity: Universitat Rovira i Virgili

Journal publication year: 2018

Publication Type: Journal Publications