PMID- 33192467
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201117
IS  - 1663-4365 (Print)
IS  - 1663-4365 (Electronic)
IS  - 1663-4365 (Linking)
VI  - 12
DP  - 2020
TI  - Connecting Alzheimer's Disease With Diabetes Mellitus Through Amyloidogenic 
      Evolvability.
PG  - 576192
LID - 10.3389/fnagi.2020.576192 [doi]
LID - 576192
AB  - Type 2 diabetes mellitus (T2DM) has been clearlylinked to oxidative stress and 
      amylin amyloidosis in pancreatic beta-cells. Yet despite extensive investigation, 
      the biological significance of this is not fully understood. Recently, we 
      proposed that Alzheimer's disease (AD)-relevant amyloidogenic proteins (APs), 
      such as amyloid-beta (Abeta) and tau, might be involved in evolvability against diverse 
      stressors in the brain. Given the analogous cellular stress environments shared 
      by both T2DM and AD, the objective of this study is to explore T2DM pathogenesis 
      from the viewpoint of amyloidogenic evolvability. Similar to AD-related APs, 
      protofibrillar amylin might confer resistance against the multiple stressors in 
      beta-cells and be transmitted to offspring to deliver stress information, in the 
      absence of which, type 1 DM (T1DM) in offspring might develop. On the contrary, 
      T2DM may be manifested through an antagonistic pleiotropy mechanism during 
      parental aging. Such evolvability-associated processes might be affected by 
      parental diabetic conditions, including T1DM and T2DM. Furthermore, the 
      T2DM-mediated increase in AD risk during aging might be attributed to an 
      interaction of amylin with AD-related APs through evolvability, in which amylin 
      protofibrillar formation presumably caused by adiponectin (APN) resistance could 
      increase protofibril formation of AD-related APs in evolvability and subsequently 
      lead to T2DM promotion of AD through antagonistic pleiotropy in aging. This 
      suggests that targeting APN combined with an anti-T2DM agent might be therapeutic 
      against neurodegeneration. Collectively, T1DM and T2DM might be linked through 
      amylin evolvability, and a better understanding of amyloidogenic evolvability 
      might also reveal clues to therapeutic interventions for AD comorbid with T2DM.
CI  - Copyright (c) 2020 Ho, Takamatsu, Wada, Sugama, Waragai, Takenouchi, Masliah and 
      Hashimoto.
FAU - Ho, Gilbert
AU  - Ho G
AD  - PCND Neuroscience Research Institute, Poway, CA, United States.
FAU - Takamatsu, Yoshiki
AU  - Takamatsu Y
AD  - Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
FAU - Wada, Ryoko
AU  - Wada R
AD  - Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
FAU - Sugama, Shuei
AU  - Sugama S
AD  - Department of Physiology, Nippon Medical School, Tokyo, Japan.
FAU - Waragai, Masaaki
AU  - Waragai M
AD  - PCND Neuroscience Research Institute, Poway, CA, United States.
FAU - Takenouchi, Takato
AU  - Takenouchi T
AD  - Institute of Agrobiological Sciences, National Agriculture and Food Research 
      Organization, Tsukuba, Japan.
FAU - Masliah, Eliezer
AU  - Masliah E
AD  - Division of Neurosciences, National Institute on Aging, National Institutes of 
      Health, Bethesda, MD, United States.
FAU - Hashimoto, Makoto
AU  - Hashimoto M
AD  - Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
LA  - eng
PT  - Journal Article
DEP - 20201028
PL  - Switzerland
TA  - Front Aging Neurosci
JT  - Frontiers in aging neuroscience
JID - 101525824
PMC - PMC7655535
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - adiponectin paradox
OT  - antagonistic pleiotropy
OT  - diabetes mellitus
OT  - evolvability
EDAT- 2020/11/17 06:00
MHDA- 2020/11/17 06:01
PMCR- 2020/01/01
CRDT- 2020/11/16 08:44
PHST- 2020/06/25 00:00 [received]
PHST- 2020/08/28 00:00 [accepted]
PHST- 2020/11/16 08:44 [entrez]
PHST- 2020/11/17 06:00 [pubmed]
PHST- 2020/11/17 06:01 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fnagi.2020.576192 [doi]
PST - epublish
SO  - Front Aging Neurosci. 2020 Oct 28;12:576192. doi: 10.3389/fnagi.2020.576192. 
      eCollection 2020.