Journal
PHARMACEUTICALS
Volume 11, Issue 1, Pages -Publisher
MDPI
DOI: 10.3390/ph11010011
Keywords
Alzheimer's; insulin resistance; amyloid; TAU; cognition; insulin receptor; type 2 diabetes
Categories
Funding
- Spanish Ministry of Science and Innovation [SAF2017-84283-R, PI2016/01, CB06/05/0024]
- European Regional Development Founds
- Generalitat de Catalunya [2014SGR-525]
- PhD scholarship FPI-MICINN [BES-2012-026083]
- CONACyT Mexico [0177594]
- CONACYT [298337]
- Doctoral Program in Sciences in Molecular Biology in Medicine, LGAC Molecular Bases of Chronic Diseases-Degenerative and its Applications [000091]
- Sao Paulo Research Foundation (FAPESP)-Brazil [2015/26084-1, 2017/13224-5]
- [MAT 2014-59134-R]
- [2014SGR-1023]
Ask authors/readers for more resources
Alzheimer's disease (AD) is progressive neurodegenerative disorder characterized by brain accumulation of the amyloid beta peptide (A beta), 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 A beta 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 A beta 42 generated in the brain would impact negatively on the hypothalamus, accelerating the peripheral symptomatology of AD. In this situation, A beta 42 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available