title: Protein misfolding and aggregation in Alzheimer's disease and type 2 diabetes mellitus.
abstract: 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 β-sheet like motifs. Although conformation of these β-sheets is common to many functional proteins, the transition from α-helix to β-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-β (Aβ) 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.
authors.forename: Ghulam M
authors.initials: GM
authors.lastname: Ashraf
authors.forename: Nigel H
authors.initials: NH
authors.lastname: Greig
authors.forename: Taqi A
authors.initials: TA
authors.lastname: Khan
authors.forename: Iftekhar
authors.initials: I
authors.lastname: Hassan
authors.forename: Shams
authors.initials: S
authors.lastname: Tabrez
authors.forename: Shazi
authors.initials: S
authors.lastname: Shakil
authors.forename: Ishfaq A
authors.initials: IA
authors.lastname: Sheikh
authors.forename: Syed K
authors.initials: SK
authors.lastname: Zaidi
authors.forename: Mohammad
authors.initials: M
authors.lastname: Akram
authors.forename: Nasimudeen R
authors.initials: NR
authors.lastname: Jabir
authors.forename: Chelaprom K
authors.initials: CK
authors.lastname: Firoz
authors.forename: Aabgeena
authors.initials: A
authors.lastname: Naeem
authors.forename: Ibrahim M
authors.initials: IM
authors.lastname: Alhazza
authors.forename: Ghazi A
authors.initials: GA
authors.lastname: Damanhouri
authors.affiliation: King Fahd Medical Research Center, King Abdulaziz University, P. O. Box 80216, Jeddah 21589, Kingdom of Saudi Arabia. gashraf@kau.edu.sa.
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Kamal
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D006801:Humans; D007382:Intermediate Filaments / Q000378:metabolism; D017510:Protein Folding; D055503:Protein Multimerization; D051844:alpha-Synuclein / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D051844:alpha-Synuclein; D016875:tau Proteins