Clinical relevance of biomarkers, new therapeutic approaches, and role of post-translational modifications in the pathogenesis of Alzheimer’s disease

Ibtisam Mumtaz, Mir Owais Ayaz, Mohamad Sultan Khan, Umar Manzoor, Mohd Azhardin Ganayee, Aadil Qadir Bhat, Ghulam Hassan Dar, Badrah S. Alghamdi, Anwar M. Hashem, Mohd Jamal Dar, Gulam Md Ashraf*, Tariq Maqbool*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

6 Citations (Scopus)

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder that causes progressive loss of cognitive functions like thinking, memory, reasoning, behavioral abilities, and social skills thus affecting the ability of a person to perform normal daily functions independently. There is no definitive cure for this disease, and treatment options available for the management of the disease are not very effective as well. Based on histopathology, AD is characterized by the accumulation of insoluble deposits of amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs). Although several molecular events contribute to the formation of these insoluble deposits, the aberrant post-translational modifications (PTMs) of AD-related proteins (like APP, Aβ, tau, and BACE1) are also known to be involved in the onset and progression of this disease. However, early diagnosis of the disease as well as the development of effective therapeutic approaches is impeded by lack of proper clinical biomarkers. In this review, we summarized the current status and clinical relevance of biomarkers from cerebrospinal fluid (CSF), blood and extracellular vesicles involved in onset and progression of AD. Moreover, we highlight the effects of several PTMs on the AD-related proteins, and provide an insight how these modifications impact the structure and function of proteins leading to AD pathology. Finally, for disease-modifying therapeutics, novel approaches, and targets are discussed for the successful treatment and management of AD.

Original languageEnglish
Article number977411
JournalFrontiers in Aging Neuroscience
Volume14
DOIs
Publication statusPublished - 7 Sept 2022
Externally publishedYes

Keywords

  • AD therapeutics
  • AD-related proteins
  • Alzheimer’s disease
  • biomarkers
  • post translational modifications

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