Molecular Insights into Therapeutic Potentials of Hybrid Compounds Targeting Alzheimer's Disease.
Ankit JanaArkadyuti BhattacharjeeSabya Sachi DasAvani SrivastavaAkshpita ChoudhuryRahul BhattacharjeeSwagata DeAsma PerveenDanish IqbalPiyush Kumar GuptaSaurabh Kumar JhaShreesh OjhaSandeep Kumar SinghJanne RuokolainenNiraj Kumar JhaKavindra Kumar KesariGhulam Md AshrafPublished in: Molecular neurobiology (2022)
Alzheimer's disease (AD) is one of the most complex progressive neurological disorders involving degeneration of neuronal connections in brain cells leading to cell death. AD is predominantly detected among elder people (> 65 years), mostly diagnosed with the symptoms of memory loss and cognitive dysfunctions. The multifarious pathogenesis of AD comprises the accumulation of pathogenic proteins, decreased neurotransmission, oxidative stress, and neuroinflammation. The conventional therapeutic approaches are limited to symptomatic benefits and are ineffective against disease progression. In recent years, researchers have shown immense interest in the designing and fabrication of various novel therapeutics comprised of naturally isolated hybrid molecules. Hybrid therapeutic compounds are developed from the combination of pharmacophores isolated from bioactive moieties which specifically target and block various AD-associated pathogenic pathways. The method of designing hybrid molecules has numerous advantages over conventional multitarget drug development methods. In comparison to in silico high throughput screening, hybrid molecules generate quicker results and are also less expensive than fragment-based drug development. Designing hybrid-multitargeted therapeutic compounds is thus a prospective approach in developing an effective treatment for AD. Nevertheless, several issues must be addressed, and additional researches should be conducted to develop hybrid therapeutic compounds for clinical usage while keeping other off-target adverse effects in mind. In this review, we have summarized the recent progress on synthesis of hybrid compounds, their molecular mechanism, and therapeutic potential in AD. Using synoptic tables, figures, and schemes, the review presents therapeutic promise and potential for the development of many disease-modifying hybrids into next-generation medicines for AD.
Keyphrases
- oxidative stress
- cell death
- induced apoptosis
- multiple sclerosis
- risk assessment
- cell cycle arrest
- cognitive decline
- machine learning
- small molecule
- signaling pathway
- endoplasmic reticulum stress
- inflammatory response
- cognitive impairment
- big data
- african american
- subarachnoid hemorrhage
- white matter
- replacement therapy
- human health
- diabetic rats
- functional connectivity
- tissue engineering