Cannabis and Cannabidiol, GLP-1 Receptors, and Autophagy: The Burgeoning Link Between Cognitive Neurodegeneration With Alzheimer's Disease and Metabolic Disorders
Year: 2026
Type: article
Abstract: formed from deoxyribonucleic acid (DNA) present on chromosome ends and maintain DNA integrity, cellular reproduction, and cellular survival.With aging, TL dysfunction ultimately leads to cellular senescence which results in organ repair failure, production of reactive oxygen species and oxidative stress, mitochondrial dysfunction, and cellular metabolic disorders.Metabolic disorders, that include diabetes mellitus (DM), are intimately tied to the onset of neurodegenerative disease and cognitive loss.Similar to neurodegenerative disorders and cognitive impairment, metabolic disease and DM are increasing in prevalence globally with the number of individuals with DM at 420 million and expected to reach 700 million individuals in the year 2045.More than 50 percent of the 4 million deaths that occur per year with DM affect individuals younger than seventy years of age.DM is a chronic and multi-systemic disorder that leads to cardiac disease, retinal cell loss, renal impairment, liver compromise, cerebral ischemia, and dementia.Financial costs for the care of individuals with DM are significant reaching $760 billion USD with an additional $70 billion USD necessary for individuals with disability and functional loss.Just in the US, these costs are more than 17 percent of the Gross Domestic Product for DM care.Multiple factors contribute to metabolic disease progression that include hypertension, high serum cholesterol, tobacco and alcohol consumption, limited physical activity, and obesity.Increased body weight with obesity affects insulin sensitivity, glucose intolerance, cerebral blood flow, aging progression, and susceptibility to infection, such as with coronavirus disease 2019 (COVID-19) in DM patients.At the cellular level, metabolic dysfunction and DM promote oxidative stress, loss of stem cell function, inflammation, glymphatic pathway dysfunction, absence of mitochondrial homeostasis, endothelial cell impairment, neuronal cell injury, myelin degradation, and changes in neurotransmitter release [6][7][8][9].As a result of these cellular processes, cognitive impairment and dementia can ensue with DM resulting in memory impairment and AD.Late-onset AD also is associated with the metabolic pathway of the ε4 allele of the apolipoprotein E (APOE-ε4) gene with the risk for developing AD becoming more than 20 times greater in individuals harboring two APOE-ε4 alleles [5,[10][11][12].APOE is critical for metabolic cellular function and is produced in the liver to control the homeostasis of lipids through the transport of cholesterol, triglycerides, and phospholipids.Although some subtypes of APOE can remove potentially toxic β-amyloid (Aβ) in the brain during AD through apoptotic programmed cell death and the exposure of cellular phosphatidylserine (PS) membranes that can attract microglia for toxin removal, APOE-ε4 does not inhibit Aβ aggregation and may add additional disability by permitting viral antigen infection.This can lead to cerebral microhemorrhages during severe acute respiratory syndrome (SARS-CoV-2) exposure with coronavirus disease 2019 (COVID-19).
Source: Discovery Medicine
Author: Kenneth Maiese
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W7125143321