PMID- 37125547
OWN - NLM
STAT- MEDLINE
DCOM- 20230606
LR  - 20230609
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Linking)
VI  - 93
IP  - 3
DP  - 2023
TI  - Insulin Resistance and Impaired Branched-Chain Amino Acid Metabolism in 
      Alzheimer's Disease.
PG  - 847-862
LID - 10.3233/JAD-221147 [doi]
AB  - The pathogenesis of Alzheimer's disease (AD) is complicated and involves multiple 
      contributing factors. Mounting evidence supports the concept that AD is an 
      age-related metabolic neurodegenerative disease mediated in part by brain insulin 
      resistance, and sharing similar metabolic dysfunctions and brain pathological 
      characteristics that occur in type 2 diabetes mellitus (T2DM) and other insulin 
      resistance disorders. Brain insulin signal pathway is a major regulator of 
      branched-chain amino acid (BCAA) metabolism. In the past several years, impaired 
      BCAA metabolism has been described in several insulin resistant states such as 
      obesity, T2DM and cardiovascular disease. Disrupted BCAA metabolism leading to 
      elevation in circulating BCAAs and related metabolites is an early metabolic 
      phenotype of insulin resistance and correlated with future onset of T2DM. Brain 
      is a major site for BCAA metabolism. BCAAs play pivotal roles in normal brain 
      function, especially in signal transduction, nitrogen homeostasis, and 
      neurotransmitter cycling. Evidence from animal models and patients support the 
      involvement of BCAA dysmetabolism in neurodegenerative diseases including 
      Huntington's disease, Parkinson's disease, and maple syrup urine disease. More 
      recently, growing studies have revealed altered BCAA metabolism in AD, but the 
      relationship between them is poorly understood. This review is focused on the 
      recent findings regarding BCAA metabolism and its role in AD. Moreover, we will 
      explore how impaired BCAA metabolism influences brain function and participates 
      in the pathogenesis of AD.
FAU - Liu, Rui
AU  - Liu R
AD  - Department of Public Health and Preventive Medicine, School of Medicine, Jianghan 
      University, Wuhan, Hubei, China.
FAU - Zhang, Lei
AU  - Zhang L
AD  - Department of Chinese Medicine, School of Medicine, Jianghan University, Wuhan, 
      Hubei, China.
FAU - You, Hao
AU  - You H
AD  - Department of Public Health and Preventive Medicine, School of Medicine, Jianghan 
      University, Wuhan, Hubei, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
RN  - 0 (Insulin)
RN  - 0 (Amino Acids, Branched-Chain)
SB  - IM
MH  - Animals
MH  - *Insulin Resistance
MH  - *Diabetes Mellitus, Type 2/metabolism
MH  - *Alzheimer Disease
MH  - *Neurodegenerative Diseases
MH  - Insulin/metabolism
MH  - Amino Acids, Branched-Chain/metabolism
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - branched-chain amino acids
OT  - insulin resistance
OT  - metabolic neurodegenerative disease
OT  - metabolism
EDAT- 2023/05/01 06:42
MHDA- 2023/06/06 06:42
CRDT- 2023/05/01 05:27
PHST- 2023/06/06 06:42 [medline]
PHST- 2023/05/01 06:42 [pubmed]
PHST- 2023/05/01 05:27 [entrez]
AID - JAD221147 [pii]
AID - 10.3233/JAD-221147 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2023;93(3):847-862. doi: 10.3233/JAD-221147.