Molecular Insights into Therapeutic Potentials of Hybrid Compounds Targeting Alzheimer’s Disease

Ankit Jana, Arkadyuti Bhattacharjee, Sabya Sachi Das, Avani Srivastava, Akshpita Choudhury, Rahul Bhattacharjee, Swagata De, Asma Perveen, Danish Iqbal, Piyush Kumar Gupta, Saurabh Kumar Jha, Shreesh Ojha, Sandeep Kumar Singh, Janne Ruokolainen, Niraj Kumar Jha, Kavindra Kumar Kesari, Ghulam Md Ashraf

Research output: Contribution to journalReview articlepeer-review

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3512-3528
Number of pages17
JournalMolecular Neurobiology
Volume59
Issue number6
DOIs
Publication statusPublished - Jun 2022

Keywords

  • Alzheimer’s disease
  • Cellular pathways
  • Neuronal molecular targets
  • Pathogenesis
  • Targeted hybrid therapeutics

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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