Shared signaling pathways in Alzheimer's and metabolic disease may point to new treatment approaches

FEBS J. 2021 Jun;288(12):3855-3873. doi: 10.1111/febs.15540. Epub 2020 Sep 10.

Abstract

'A peculiar severe disease process of the cerebral cortex' are the exact words used by A. Alzheimer in 1906 to describe a patient's increasingly severe condition of memory loss, changes in personality, and sleep disturbance. A century later, this 'peculiar' disease has become widely known as Alzheimer's disease (AD), the world's most common neurodegenerative disease, affecting more than 35 million people globally. At the same time, its pathology remains unclear and no successful treatment exists. Several theories for AD etiology have emerged throughout the past century. In this review, we focus on the metabolic mechanisms that are similar between AD and metabolic diseases, based on the results from genome-wide association studies. We discuss signaling pathways involved in both types of disease and look into new optogenetic methods to study the in vivo mechanisms of AD.

Keywords: Alzheimer’s disease; amyloid-β; lipids; metabolic disease; optogenetics; signal transduction; type 2 diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism*
  • Cerebral Cortex / pathology
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / pathology
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Gene Expression Regulation
  • Glucose / metabolism*
  • Glycogen Synthase Kinase 3 beta / genetics
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Humans
  • Insulin / metabolism
  • Insulin Resistance
  • Metformin / therapeutic use
  • Neuroprotective Agents / therapeutic use*
  • Optogenetics / methods
  • Oxidative Stress / drug effects
  • Signal Transduction / drug effects
  • Signal Transduction / genetics*
  • Sulfonylurea Compounds / therapeutic use
  • tau Proteins / genetics
  • tau Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • Dipeptidyl-Peptidase IV Inhibitors
  • Insulin
  • MAPT protein, human
  • Neuroprotective Agents
  • Sulfonylurea Compounds
  • tau Proteins
  • Metformin
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Glucose