Cysteine in Alzheimer's Disease: Redox Regulation of Protein Functions

Cysteine in Alzheimer's Disease: Redox Regulation of Protein Functions

Suvarna P. Ingale (Indira College of Pharmacy, India), Rupali Patil (Sir Dr. M. S. Gosavi College of Pharmaceutical Education and Research, India) and Aman B. Upaganlawar (SNJB's SSDJ College of Pharmacy, Chandwad, Nashik, India)
Copyright: © 2020 |Pages: 28
DOI: 10.4018/978-1-7998-1317-0.ch013


Alzheimer's disease (AD) is characterized by selective loss of neurons in the hippocampus and neocortex due to abnormalities in proteins, mainly Aβ peptide and tau protein, in the form of abnormal protein aggregations or depositions in neurons. Recently oxidative/nitrosative stress has been identified as an important facilitator of neurodegeneration in AD. Cysteine-dependent proteins are known to be associated with the neurodegenerative process. Such cysteine-dependent enzyme proteins are proteases, antioxidant enzymes, kinases, phosphatases, and also non-enzymatic proteins such that utilize cysteine as a structural part of the catalytic site. This chapter deals with the role of cysteine in handling reactive oxygen/nitrogen species during oxidative/nitrosative stress and posttranslational modification of proteins causing protein misfolding or protein aggregation during neurodegeneration associated with AD.
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Alzheimer’s disease (AD) is a continuously advancing, devastating, prolonged neurodegenerative disorder chiefly manifested as amnesia limiting the patient's ability to perform daily activities, affecting mainly the elderly population above 60 years of age (Kumar et al., 2015; Masters et al., 2018). According to Alzheimer’s Disease International (ADI), there will be one fresh incident of AD per 3 seconds globally. It was estimated that in 2018, globally 50 million people are suffering from AD and the cost of its management is US$ 1 trillion. By 2050, this incidence will be above threefold to 152 million with cost upswing to US$ 2 trillion (Alzheimer’s Disease International, 2018). According to the age of onset, AD is of two types, early-onset AD (EOAD) and late-onset AD (LOAD). EOAD affects around 1 to 6 present of all cases in the age range of thirty to sixty years, while the onset of LOAD is after sixty or sixty-five years (David et al., 2005). AD share a strong genetic basis that distinguishes AD into two genetically diverse forms such as familial AD (FAD) and sporadic AD (SAD). FAD exhibit autosomal dominant inheritance (Ray et al., 1998). While, SAD exhibit environmental and genetic differences as major risk factors without the involvement of autosomal-dominant inheritance (Braak and Tredici, 2012).

Aging is the utmost imperative risk factor of AD. Succeeding aging, the occurrence of the apolipoprotein E ε4 (ApoE ε4) allele is one more major risk factor (Dong et al, 2012). The lifetime risk of AD in an individual without an ApoE ε4 is 9% which increases to 29% in individuals with at least 1 ε4 allele (Seshadri et al., 1995). Other suspected risk factors of AD include cardiovascular disease, traumatic brain injury, depression, lower educational and/or occupational strata, parental age at time of birth, smoking, first-degree relative with Down syndrome, low levels of folate and vitamin B12, and elevated plasma and total homocysteine levels (David et al., 2005).

AD is manifested in the form of clinical dementia syndrome which is mixed and diverse. The signs and symptoms differ with the advancement and chronicity of the illness. The hallmark manifestation of the clinical dementia syndrome is progressive intellectual deterioration with invariable memory loss leading to the inability to perform and function in the normal milieu (Burns and lliffe, 2009). Also, other cognitive functions are affected which comprise the language, visuospatial, judgment, appreciation, planning, organizing and decision-making problems. Along with cognitive impairment, AD is universally presented with non-cognitive neuropsychiatric symptoms (Förstl and Kurz, 1998) viz. behavioral disturbance (lethargy, violence, nervousness, disinhibition and abnormal motor behavior), altered mood (despair, apprehension, and irritability), psychomotor disturbance (disturbed sleep and appetite), perceptual disturbance (misconceptions, hallucinations, misapprehensions) (Salami and Lyketsos, 2011). Many researchers clinically have characterized AD by deposition of the Aβ peptide plaque mainly within and around arterioles and twisted bundles of aggregated tau within the neurons. Literature evidence supports the concept of injurious participation of oxidative and nitrosative stress in the initiation and progression of AD in the form of two most important pathological markers of AD i.e. abnormal deposition of beta amyloid (Aβ) plaques and neurofibrillary tangles (NFTs) of tau proteins.

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