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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

A Recent Update on Pathophysiology and Therapeutic Interventions of Alzheimer’s Disease

Author(s): Mohd. Kashif, Prathibha Sivaprakasam, Poornima Vijendra, Mohammad Waseem and Ashok Kumar Pandurangan*

Volume 29, Issue 43, 2023

Published on: 30 November, 2023

Page: [3428 - 3441] Pages: 14

DOI: 10.2174/0113816128264355231121064704

Price: $65


Aim: Alzheimer’s disease (AD) has been identified as a progressive brain disorder associated with memory dysfunction and the accumulation of β-amyloid plaques and neurofibrillary tangles of τ protein. Mitochondria is crucial in maintaining cell survival, cell death, calcium regulation, and ATP synthesis. Mitochondrial dysfunction and linked calcium overload have been involved in the pathogenesis of AD. CRM2 (Collapsin response mediator protein-2) is involved in endosomal lysosomal trafficking as well as autophagy, and their reduced level is also a primary culprit in the progression of AD. In addition, Cholinergic neurotransmission and neuroinflammation are two other mechanisms implicated in AD onset and might be protective targets to attenuate disease progression. The microbiota-gut-brain axis (MGBA) is another crucial target for AD treatment. Crosstalk between gut microbiota and brain mutually benefitted each other, dysbiosis in gut microbiota affects the brain functions and leads to AD progression with increased AD-causing biomarkers. Despite the complexity of AD, treatment is only limited to symptomatic management. Therefore, there is an urgent demand for novel therapeutics that target associated pathways responsible for AD pathology. This review explores the role of different mechanisms involved in AD and possible therapeutic targets to protect against disease progression.

Background: Amidst various age-related diseases, AD is the most deleterious neurodegenerative disorder that affects more than 24 million people globally. Every year, approximately 7.7 million new cases of dementia have been reported. However, to date, no novel disease-modifying therapies are available to treat AD.

Objective: The aim of writing this review is to highlight the role of key biomarker proteins and possible therapeutic interventions that could play a crucial role in mitigating the ongoing prognosis of Alzheimer’s disease.

Materials and Methods: The available information about the disease was collected through multiple search engines, including PubMed, Science Direct, Clinical Trials, and Google Scholar.

Results: Accumulated pieces of evidence reveal that extracellular aggregation of β-amyloid plaques and intracellular tangles of τ protein are peculiar features of perpetuated Alzheimer’s disease (AD). Further, the significant role of mitochondria, calcium, and cholinergic pathways in the pathogenesis of AD makes the respiratory cell organelle a crucial therapeutic target in this neurodegenerative disease. All currently available drugs either delay the clinical damage to cells or temporarily attenuate some symptoms of Alzheimer’s disease.

Conclusion: The pathological features of AD are extracellular deposition of β-amyloid, acetylcholinesterase deregulation, and intracellular tangles of τ protein. The multifactorial heterogeneity of disease demands more research work in this field to find new therapeutic biological targets.

Keywords: Neurodegenerative disorders, Alzheimer’s disease, dementia, β-amyloid, τ protein, acetylcholinesterase, MCU, NCLX.

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