PMID- 32450345
OWN - NLM
STAT- MEDLINE
DCOM- 20210706
LR  - 20210706
IS  - 1096-1186 (Electronic)
IS  - 1043-6618 (Linking)
VI  - 159
DP  - 2020 Sep
TI  - Proteotoxicity and mitochondrial dynamics in aging diabetic brain.
PG  - 104948
LID - S1043-6618(20)31256-1 [pii]
LID - 10.1016/j.phrs.2020.104948 [doi]
AB  - Impaired neuronal proteostasis is a salient feature of both aging and protein 
      misfolding disorders. Amyloidosis, a consequence of this phenomena is observed in 
      the brains of diabetic patients over the chronic time period. These toxic 
      aggregates not only cause age-related decline in proteostasis, but also dwindle 
      its ability to increase or restore the chaperones in response to any stressful 
      condition. Mitochondria acts as the main source of energy regulation and many 
      metabolic disorders such as diabetes have been associated with altered oxidative 
      phosphorylation (OxPhos) and redox imbalance in the mitochondria. The 
      mitochondrial unfolded protein response (UPR(mt)) acts as a mediator for 
      maintaining the mitochondrial protein homeostasis and quality control during such 
      conditions. Over a long time period, these responses start shutting off leading 
      to proteotoxic stress in the neurons. This reduces the buffering capacity of 
      protein network signalling during aging, thereby increasing the risk of 
      neurodegeneration in the brain. In this review, we focus on the proteotoxic 
      stress that occurs as an amalgamation of diabetes and aging, as well as the 
      impact of mitochondrial dysfunction on the neuronal survival affecting the 
      diabetic brain and its long term consequences on the memory changes.
CI  - Copyright (c) 2020. Published by Elsevier Ltd.
FAU - Fernandes, Valencia
AU  - Fernandes V
AD  - Department of Pharmacology and Toxicology, National Institute of Pharmaceutical 
      Education and Research (NIPER), Hyderabad, Telangana, 500037, India.
FAU - Choudhary, Mamta
AU  - Choudhary M
AD  - Department of Pharmacology and Toxicology, National Institute of Pharmaceutical 
      Education and Research (NIPER), Hyderabad, Telangana, 500037, India.
FAU - Kumar, Ashutosh
AU  - Kumar A
AD  - Department of Pharmacology and Toxicology, National Institute of Pharmaceutical 
      Education and Research (NIPER), Hyderabad, Telangana, 500037, India.
FAU - Singh, Shashi Bala
AU  - Singh SB
AD  - Department of Pharmacology and Toxicology, National Institute of Pharmaceutical 
      Education and Research (NIPER), Hyderabad, Telangana, 500037, India. Electronic 
      address: drshashisingh@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20200522
PL  - Netherlands
TA  - Pharmacol Res
JT  - Pharmacological research
JID - 8907422
RN  - 0 (Blood Glucose)
RN  - 0 (DNA, Mitochondrial)
SB  - IM
MH  - Age Factors
MH  - Aging/*metabolism/pathology/psychology
MH  - Animals
MH  - Blood Glucose/metabolism
MH  - Brain/*metabolism/pathology
MH  - DNA, Mitochondrial/genetics/metabolism
MH  - Diabetes Complications/genetics/*metabolism/pathology/psychology
MH  - Energy Metabolism
MH  - Humans
MH  - Memory
MH  - Mitochondria/genetics/*metabolism/pathology
MH  - *Mitochondrial Dynamics
MH  - Nerve Degeneration
MH  - Neurodegenerative Diseases/genetics/*metabolism/pathology/psychology
MH  - Neurons/*metabolism/pathology
MH  - Protein Unfolding
MH  - *Proteostasis
MH  - Signal Transduction
OTO - NOTNLM
OT  - Aging
OT  - Diabetes
OT  - Mitochondrial biogenesis
OT  - Mitochondrial unfolded protein response (UPRmt)
OT  - Mitophagy
OT  - Proteotoxicity
EDAT- 2020/05/26 06:00
MHDA- 2021/07/07 06:00
CRDT- 2020/05/26 06:00
PHST- 2020/02/18 00:00 [received]
PHST- 2020/05/07 00:00 [revised]
PHST- 2020/05/19 00:00 [accepted]
PHST- 2020/05/26 06:00 [pubmed]
PHST- 2021/07/07 06:00 [medline]
PHST- 2020/05/26 06:00 [entrez]
AID - S1043-6618(20)31256-1 [pii]
AID - 10.1016/j.phrs.2020.104948 [doi]
PST - ppublish
SO  - Pharmacol Res. 2020 Sep;159:104948. doi: 10.1016/j.phrs.2020.104948. Epub 2020 
      May 22.