PMID- 32170854
OWN - NLM
STAT- MEDLINE
DCOM- 20210624
LR  - 20210624
IS  - 2162-3279 (Electronic)
VI  - 10
IP  - 5
DP  - 2020 May
TI  - Neurodegeneration in type 2 diabetes: Alzheimer's as a case study.
PG  - e01577
LID - 10.1002/brb3.1577 [doi]
LID - e01577
AB  - INTRODUCTION: Rigorous research in the last few years has shown that in addition 
      to the classical mechanism of neurodegeneration, certain unconventional 
      mechanisms may also lead to neurodegenerative disease. One of them is a widely 
      studied metabolic disorder: type 2 diabetes mellitus (T2DM). We now have a clear 
      understanding of glucose-mediated neurodegeneration, mostly from studies in 
      Alzheimer's disease (AD) models. AD is recognized to be significantly associated 
      with hyperglycemia, even earning the term "type 3 diabetes." Here, we review 
      first the pathophysiology of AD, both from the perspective of classical protein 
      accumulation, as well as the newer T2DM-dependent mechanisms supported by 
      findings from patients with T2DM. Secondly, we review the different pathways 
      through which neurodegeneration is aggravated in hyperglycemic conditions taking 
      AD as a case study. Finally, some of the current advances in AD management as a 
      result of recent research developments in metabolic disorders-driven 
      neurodegeneration are also discussed. METHODS: Relevant literatures found from 
      PubMed search were reviewed. RESULTS: Apart from the known causes of AD, type 2 
      diabetes opens a new window to the AD pathology in several ways. It is a 
      bidirectional interaction, of which, the molecular and signaling mechanisms are 
      recently studied. This is our attempt to connect all of them to draw a complete 
      mechanistic explanation for the neurodegeneration in T2DM. Refer to Figure 3. 
      CONCLUSION: The perspective of AD as a classical neurodegenerative disease is 
      changing, and it is now being looked at from a zoomed-out perspective. The 
      correlation between T2DM and AD is something observed and studied extensively. It 
      is promising to know that there are certain advances in AD management following 
      these studies.
CI  - (c) 2020 Indian Institute of Science Education and Research (IISER), Tirupati. 
      Brain and Behavior published by Wiley Periodicals, Inc.
FAU - Madhusudhanan, Jalaja
AU  - Madhusudhanan J
AD  - Department of Biology, Indian Institute of Science Education and Research (IISER) 
      Tirupati, Tirupati, India.
FAU - Suresh, Gowthaman
AU  - Suresh G
AD  - Department of Biology, Indian Institute of Science Education and Research (IISER) 
      Tirupati, Tirupati, India.
FAU - Devanathan, Vasudharani
AU  - Devanathan V
AUID- ORCID: 0000-0002-2052-400X
AD  - Department of Biology, Indian Institute of Science Education and Research (IISER) 
      Tirupati, Tirupati, India.
LA  - eng
GR  - Indian Institute of Science Education and Research (IISER), 
      Tirupati/International
GR  - DST-SERB/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20200314
PL  - United States
TA  - Brain Behav
JT  - Brain and behavior
JID - 101570837
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - *Alzheimer Disease
MH  - *Diabetes Mellitus, Type 2/complications
MH  - Glucose
MH  - Humans
MH  - *Hyperglycemia
MH  - *Neurodegenerative Diseases
PMC - PMC7218246
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - neurodegeneration
OT  - type 2 diabetes mellitus
OT  - type 3 diabetes
COIS- Authors declare no conflicts of interest.
EDAT- 2020/03/15 06:00
MHDA- 2021/06/25 06:00
PMCR- 2020/03/14
CRDT- 2020/03/15 06:00
PHST- 2019/07/17 00:00 [received]
PHST- 2020/01/04 00:00 [accepted]
PHST- 2020/03/15 06:00 [pubmed]
PHST- 2021/06/25 06:00 [medline]
PHST- 2020/03/15 06:00 [entrez]
PHST- 2020/03/14 00:00 [pmc-release]
AID - BRB31577 [pii]
AID - 10.1002/brb3.1577 [doi]
PST - ppublish
SO  - Brain Behav. 2020 May;10(5):e01577. doi: 10.1002/brb3.1577. Epub 2020 Mar 14.