Possible Role of Activin in the Adiponectin Paradox-Induced Progress of Alzheimer’s Disease

Abstract

Accumulating evidence suggests that the adiponectin (APN) paradox might be involved in promoting aging-associated chronic diseases such as Alzheimer’s disease (AD). In human brain, APN regulation of the evolvability of amyloidogenic proteins (APs), including amyloid-β (Aβ) and tau, in developmental/reproductive stages, might be paradoxically manifest as APN stimulation of AD through antagonistic pleiotropy in aging. The unique mechanisms underlying APN activity remain unclear, a better understanding of which might provide clues for AD therapy. In this paper, we discuss the possible relevance of activin, a member of transforming growth factor β (TGFβ) superfamily of peptides, to antagonistic pleiotropy effects of APN. Notably, activin, a multiple regulator of cell proliferation and differentiation, as well as an endocrine modulator in reproduction and an organizer in early development, might promote aging-associated disorders, such as inflammation and cancer. Indeed, serum activin, but not serum TGFβ increases during aging. Also, activin/TGFβ signal through type II and type I receptors, both of which are transmembrane serine/threonine kinases, and the serine/threonine phosphorylation of APs, including Aβ 42 serine 8 and αS serine 129, may confer pathological significance in neurodegenerative diseases. Moreover, activin expression is induced by APN in monocytes and hepatocytes, suggesting that activin might be situated downstream of the APN paradox. Finally, a meta-analysis of genome-wide association studies demonstrated that two SNPs relevant to the activin/TGFβ receptor signaling pathways conferred risk for major aging-associated disease. Collectively, activin might be involved in the APN paradox of AD and could be a significant therapeutic target.

Investigating the relationship between infertility and depression in women

“…Many studies show increased stress, anxiety and depression in today's society, followed by infertility in women. The prevalence of depression and stress is high in infertile women (Hashimoto et al, 2021;Lambert-Messerlian & Harlow, 2006). These increases have prolonged infertility and also caused damage to marital relationships, reducing mental health and quality of life (Berg & Wilson, 1991;Sargolzaee et al, 2001).…”

Adiponectin Modulation by Genotype and Maternal Choline Supplementation in a Mouse Model of Down Syndrome and Alzheimer’s Disease

“…Moreover, preclinical and clinical trials are required to determine if MCS will be beneficial in the context of MetS/IR and/or T2DM, including in the study of leptin-based and insulin-derived models of diabetes [115,116]. Additional treatments affecting APN and downstream activators include Os-pep, a novel nonapeptide APN mimetic, which binds to APN receptors [101] and activin, which may be a potential therapeutic target for reduction of amyloidogenic proteins during AD progression [117].…”

Serum Adiponectin and In Vivo Brain Amyloid Deposition in Cognitively Normal Older Adults: A Cohort Study

“…From this point of views on linking AD and dysfunctional adipose tissue and adipokines, adiponectin has been proposed as a new clue to understand the pathogenesis of AD [4,[7][8][9][10][11]. Adiponectin [12], a collagen-like 30 kDa protein hormone, is the most abundant adipokine in circulation, representing 0.01% of the total plasma proteins in humans [13].…”

“…Increasing evidence suggests that Alzheimer’s disease (AD), the most common cause of dementia, is a brain metabolic disorder which is intrinsically linked to adipose tissue dysfunction and adipokines-mediated signals [ 1 - 6 ]. From this point of views on linking AD and dysfunctional adipose tissue and adipokines, adiponectin has been proposed as a new clue to understand the pathogenesis of AD [ 4 , 7 - 11 ]. Adiponectin [ 12 ], a collagen-like 30 kDa protein hormone, is the most abundant adipokine in circulation, representing 0.01% of the total plasma proteins in humans [ 13 ].…”