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.
Keywords: Alzheimer's disease, amylin, amyloid-β, amyloid precursor protein, islet amyloid polypeptide, neurofibrillary
tangles, Parkinson's disease, protein folding, proteostasis, tau, tauopathy, type 2 diabetes mellitus, α-synuclein.
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