Current Strategies and Novel Drug Approaches for Alzheimer Disease

Abstract

Background: Alzheimer’s disease (AD) is a chronic devastating dysfunction of neurons in the brain leading to dementia. It mainly arises due to neuronal injury in the cerebral cortex and hippocampus area of the brain and is clinically manifested as a progressive mental failure, disordered cognitive functions, personality changes, reduced verbal fluency and impairment of speech. The pathology behind AD is the formation of intraneuronal fibrillary tangles, deposition of amyloid plaque and decline in choline acetyltransferase and loss of cholinergic neurons. Tragically, the disease cannot be cured but its progression can be halted. Various cholinesterase inhibitors available in the market like Tacrine, Donepezil, Galantamine, Rivastigmine, etc are being used to manage the symptoms of Alzheimer’s disease. Objective: The paper’s objective is to throw light not only on the cellular/genetic basis of the disease, but also on the current trends and various strategies of treatment including the use of phytopharmaceuticals and nutraceuticals. Materials & Methods: Enormous literature survey was conducted and published articles of PUBMED, Scifinder, Google Scholar, Clinical Trials.org and Alzheimer Association reports were studied intensively to consolidate the information on the strategies available to combat Alzheimer’s disease. Results & Conclusion: Currently, several strategies are being investigated for the treatment of Alzheimer’s disease. Immunotherapies targeting amyloid-beta plaques, tau protein and neural pathways are undergoing clinical trials. Moreover, antisense oligonucleotide methodologies are being approached as therapies for its management. Phytopharmaceuticals and nutraceuticals are also gaining attention in overcoming the symptoms related to AD. The present review article concludes that novel and traditional therapies simultaneously promise future hope for AD treatment.

Prospects of Marine Sterols against Pathobiology of Alzheimer’s Disease: Pharmacological Insights and Technological Advances

“…Alzheimer's disease (AD) is a devastating chronic neurodegenerative disorder characterized by intracellular aggregations of tau protein in neurofibrillary tangles (NFTs) formation and extracellular amyloid β-protein (Aβ) accumulation as the formation of a senile plaque in the specific brain regions [1,2]. About 70% of AD risk is found to be based on genetic predisposition, although numerous genes participate and its real causes in addition to molecular mechanisms have not been clearly elucidated [2][3][4]. However, aggregation of misfolded proteins could result in AD pathogenesis [5], and the extracellular domain along with a small cytosolic domain present in amyloid β-protein precursor (APP) is the key molecular driver of AD pathogenesis [6].…”

Prospective Application of Two New Pyridine-Based Zinc (II) Amide Carboxylate in Management of Alzheimer’s Disease: Synthesis, Characterization, Computational and in vitro Approaches

“…It is ranked as the sixth leading cause of death in the US. 4 Over 50 million individuals globally are thought to have dementia, with around 10 million instances identified every day. 5 Several hypotheses are proposed regarding Alzheimer's disease, including the Aβ amyloid hypothesis, Aβ amyloid oligomer hypothesis, Presenilin hypothesis, Calcium dysfunction hypothesis, lysosome hypothesis, and the Tau hypothesis.…”

Modulatory Effects of Autophagy on APP Processing as a Potential Treatment Target for Alzheimer’s Disease

“…Alzheimer’s disease (AD) is the most irreversible and progressive brain disorder of neurodegenerative disease characterized by the accumulation of extracellular amyloid beta (Aβ) leading to the formation of senile plaques and intracellular tau aggregates that form neurofibrillary tangles (NFTs) in the brain [ 1 , 2 ]. Approximately, 70% of AD risk is considered to be inherited and numerous genes are frequently involved, although the actual cause and molecular mechanisms are poorly understood [ 2 , 3 , 4 ]. Amyloid precursor protein (APP), a transmembrane glycoprotein (type I), is the key molecular driver of AD pathogenesis.…”