PMID- 25230234
OWN - NLM
STAT- MEDLINE
DCOM- 20150713
LR  - 20211021
IS  - 1996-3181 (Electronic)
IS  - 1871-5273 (Print)
IS  - 1871-5273 (Linking)
VI  - 13
IP  - 7
DP  - 2014
TI  - Protein misfolding and aggregation in Alzheimer's disease and type 2 diabetes 
      mellitus.
PG  - 1280-93
AB  - In general, proteins can only execute their various biological functions when 
      they are appropriately folded. Their amino acid sequence encodes the relevant 
      information required for correct three-dimensional folding, with or without the 
      assistance of chaperones. The challenge associated with understanding protein 
      folding is currently one of the most important aspects of the biological 
      sciences. Misfolded protein intermediates form large polymers of unwanted 
      aggregates and are involved in the pathogenesis of many human diseases, including 
      Alzheimer's disease (AD) and Type 2 diabetes mellitus (T2DM). AD is one of the 
      most prevalent neurological disorders and has worldwide impact; whereas T2DM is 
      considered a metabolic disease that detrementally influences numerous organs, 
      afflicts some 8% of the adult population, and shares many risk factors with AD. 
      Research data indicates that there is a widespread conformational change in the 
      proteins involved in AD and T2DM that form beta-sheet like motifs. Although 
      conformation of these beta-sheets is common to many functional proteins, the 
      transition from alpha-helix to beta-sheet is a typical characteristic of amyloid 
      deposits. Any abnormality in this transition results in protein aggregation and 
      generation of insoluble fibrils. The abnormal and toxic proteins can interact 
      with other native proteins and consequently catalyze their transition into the 
      toxic state. Both AD and T2DM are prevalent in the aged population. AD is 
      characterized by the accumulation of amyloid-beta (Abeta) in brain, while T2DM is 
      characterized by the deposition of islet amyloid polypeptide (IAPP, also known as 
      amylin) within beta-cells of the pancreas. T2DM increases pathological 
      angiogenesis and immature vascularisation. This also leads to chronic cerebral 
      hypoperfusion, which results in dysfunction and degeneration of neuroglial cells. 
      With an abundance of common mechanisms underpinning both disorders, a significant 
      question that can be posed is whether T2DM leads to AD in aged individuals and 
      the associations between other protein misfolding diseases.
FAU - Ashraf, Ghulam M
AU  - Ashraf GM
FAU - Greig, Nigel H
AU  - Greig NH
FAU - Khan, Taqi A
AU  - Khan TA
FAU - Hassan, Iftekhar
AU  - Hassan I
FAU - Tabrez, Shams
AU  - Tabrez S
FAU - Shakil, Shazi
AU  - Shakil S
FAU - Sheikh, Ishfaq A
AU  - Sheikh IA
FAU - Zaidi, Syed K
AU  - Zaidi SK
FAU - Akram, Mohammad
AU  - Akram M
FAU - Jabir, Nasimudeen R
AU  - Jabir NR
FAU - Firoz, Chelaprom K
AU  - Firoz CK
FAU - Naeem, Aabgeena
AU  - Naeem A
FAU - Alhazza, Ibrahim M
AU  - Alhazza IM
FAU - Damanhouri, Ghazi A
AU  - Damanhouri GA
FAU - Kamal, Mohammad A
AU  - Kamal MA
AD  - King Fahd Medical Research Center, King Abdulaziz University, P. O. Box 80216, 
      Jeddah 21589, Kingdom of Saudi Arabia. gashraf@kau.edu.sa.
LA  - eng
GR  - ZIA AG000311-13/Intramural NIH HHS/United States
GR  - ZIA AG000311-14/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
PL  - United Arab Emirates
TA  - CNS Neurol Disord Drug Targets
JT  - CNS & neurological disorders drug targets
JID - 101269155
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (alpha-Synuclein)
RN  - 0 (tau Proteins)
SB  - IM
MH  - Alzheimer Disease/*metabolism
MH  - Amyloid beta-Peptides/metabolism
MH  - Animals
MH  - Diabetes Mellitus, Type 2/*metabolism
MH  - Humans
MH  - Intermediate Filaments/metabolism
MH  - Protein Folding
MH  - Protein Multimerization
MH  - alpha-Synuclein/metabolism
MH  - tau Proteins/metabolism
PMC - PMC5193501
MID - NIHMS837363
COIS- The authors confirm that this article content has no conflict of interest.
EDAT- 2014/09/18 06:00
MHDA- 2015/07/15 06:00
PMCR- 2016/12/28
CRDT- 2014/09/18 06:00
PHST- 2014/04/20 00:00 [received]
PHST- 2014/05/11 00:00 [revised]
PHST- 2014/05/12 00:00 [accepted]
PHST- 2014/09/18 06:00 [entrez]
PHST- 2014/09/18 06:00 [pubmed]
PHST- 2015/07/15 06:00 [medline]
PHST- 2016/12/28 00:00 [pmc-release]
AID - CNSNDDT-EPUB-62371 [pii]
AID - 10.2174/1871527313666140917095514 [doi]
PST - ppublish
SO  - CNS Neurol Disord Drug Targets. 2014;13(7):1280-93. doi: 
      10.2174/1871527313666140917095514.