The Danger of Being Too Sympathetic: Norepinephrine in Alzheimer's Disease and Graying of Hair
| Autor: | Andrew R Mendelsohn, James W Larrick |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Aging Sympathetic nervous system animal structures Adrenergic receptor tau Proteins Norepinephrine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Alzheimer Disease Animals Humans Medicine Phosphorylation Neurotransmitter Amyloid beta-Peptides business.industry Stem Cells Neurotoxicity Hair follicle medicine.disease Mice Inbred C57BL Autonomic nervous system Phenotype 030104 developmental biology medicine.anatomical_structure chemistry Geriatrics and Gerontology business Hair Follicle Pigmentation Disorders Idazoxan Neuroscience Stress Psychological 030217 neurology & neurosurgery Hair Signal Transduction medicine.drug |
| Zdroj: | Rejuvenation Research. 23:68-72 |
| ISSN: | 1557-8577 1549-1684 |
| DOI: | 10.1089/rej.2020.2309 |
| Popis: | Although alterations in the sympathetic nervous system (SNS) with age have been reported, and serious degenerative diseases of the autonomic nervous system such as multiple system atrophy are more likely to strike older people, connections between dysregulated adrenergic receptors and age-associated diseases and phenotypes have not been well studied. Two recent reports suggest that SNS may be more closely connected than previously appreciated. First, low nanomolar concentrations of Alzheimer's disease (AD)-associated Aβ42-amyloid oligomers alter signaling by SNS neurotransmitter norepinephrine (NE) to sufficiently activate kinase GSK3β to hyperphosphorylate tau, a key mediator of neurotoxicity in AD. Connecting beta-amyloid to tau in AD has been a key quest in understanding AD and developing therapeutics. The α2 adrenergic receptor inhibitory drug idazoxan reduces GSK3β activity and tau phosphorylation in AD mice with improved cognitive function, even in the presence of beta-amyloid deposits. In this study, SNS activation in the brain coupled with problematic Aβ42-amyloid oligomers result in serious consequences that can be ameliorated by reducing SNS signaling. A second example of the detrimental effects of increased SNS signaling is the premature graying of hair in response to stress. Secretion of NE resulting from stress causes differentiation of most hair pigment melanocyte stem cells (MeSCs) into melanocytes, rapidly depleting the hair follicle of pigment-producing cells as mature melanocytes undergo apoptosis and MeSCs are eventually eliminated. Blockade of NE SNS signaling preserves hair coloration in stressed animals. Increased SNS activation has serious apparently irreversible effects on homeostasis in both situations. Although neither report directly addresses aging, given that AD and the loss of hair pigmentation have strong age associations, it is of interest to better understand the role that SNS has in promoting age-associated phenotypes generally and determine if tuning the SNS through drug-mediated attenuation of SNS signaling may be of medical benefit. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|