Aging-Related Protein Alterations in the Brain

Issue title: Pro-Oxidants and Antioxidants in Alzheimer’s Disease

Guest editors: Pravat K. Mandal

Article type: Review Article

Authors: Syed, Rafay Ali^{a; b} | Hayat, Mahnoor^{a; c} | Qaiser, Hammad^a | Uzair, Mohammad^a | Al-Regaiey, Khalid^d | Khallaf, Roaa^e | Kaleem, Imdad^f | Bashir, Shahid^{g; *}

Affiliations: [a] Department of Biological Sciences, Faculty of Basic & Applied Sciences, International Islamic University Islamabad, Pakistan | [b] Department of Biotechnology, Quaid-i-Azam University, Islamabad, Pakistan | [c] Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Islamabad, Pakistan | [d] Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia | [e] Department of Neurology, Neuroscience Center, King Fahad Specialist Hospital, Dammam, Saudi Arabia | [f] Department of Biosciences, COMSATS University, Islamabad, Pakistan | [g] Neuroscience Center, King Fahad Specialist Hospital Dammam, Dammam, Saudi Arabia

Correspondence: [*] Correspondence to: Shahid Bashir, Neuroscience Center, King Fahad Specialist Hospital ammam, Dammam, Saudi Arabia. E-mail: [email protected].

Abstract: Aging is an intrinsic aspect of an organism’s life cycle and is characterized by progressive physiological decline and increased susceptibility to mortality. Many age-associated disorders, including neurological disorders, are most commonly linked with the aging process, such as Alzheimer’s disease (AD). This review aims to provide a comprehensive overview of the effects of aging and AD on the molecular pathways and levels of different proteins in the brain, including metalloproteins, neurotrophic factors, amyloid proteins, and tau proteins. AD is caused by the aggregation of amyloid proteins in the brain. Factors such as metal ions, protein ligands, and the oligomerization state of amyloid precursor protein significantly influence the proteolytic processing of amyloid-β protein precursor (AβPP). Tau, a disordered cytosolic protein, serves as the principal microtubule-associated protein in mature neurons. AD patients exhibit decreased levels of nerve growth factor within their nervous systems and cerebrospinal fluid. Furthermore, a significant increase in brain-derived neurotrophic factor resulting from the neuroprotective effect of glial cell line-derived neurotrophic factor suggests that the synergistic action of these proteins plays a role in inhibiting neuronal degeneration and atrophy. The mechanism through which Aβ and AβPP govern Cu2+ transport and their influence on Cu2+ and other metal ion pools requires elucidation in future studies. A comprehensive understanding of the influence of aging and AD on molecular pathways and varying protein levels may hold the potential for the development of novel diagnostic and therapeutic methods for the treatment of AD.

Keywords: Alzheimer’s disease, apoptosis, brain-derived neurotrophic factor, neurotrophic factors, oxidative stress

DOI: 10.3233/JAD-230801

Journal: Journal of Alzheimer's Disease, vol. 99, no. s1, pp. S5-S22, 2024