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Basic Science and Pathogenesis.

Priyam Ghosh1

  • 1IIT Guwahati, Guwahati, Assam, India.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
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Novel benzimidazole-derived probes offer a dual approach for Alzheimer's disease (AD). These agents detect amyloid-beta (Aβ) plaques and therapeutically reduce Aβ aggregation and oxidative stress, aiding early diagnosis and treatment.

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Area of Science:

  • Neuroscience
  • Materials Science
  • Biochemistry

Background:

  • Alzheimer's disease (AD) is a progressive neurological disorder marked by cognitive decline and amyloid-beta (Aβ) plaque accumulation.
  • Current treatments for AD are limited, highlighting the urgent need for advanced diagnostic and therapeutic solutions.

Purpose of the Study:

  • To design, synthesize, and evaluate novel multifunctional benzimidazole-derived photoactivable probes for Alzheimer's disease.
  • To explore the theranostic potential of these probes in interacting with Aβ aggregates and inhibiting Aβ fibril formation.

Main Methods:

  • Rational design and synthesis of benzimidazole-derived photoactivable aggregation-induced emission (AIE) probes.
  • Evaluation of probe interaction with Aβ aggregates, including inhibition of fibril formation and photo-oxygenation.
  • Assessment of probes' ability to chelate metal ions, scavenge reactive oxygen species (ROS), and mitigate oxidative stress.

Main Results:

  • Benzimidazole-functionalized probes demonstrated interaction with Aβ aggregates, reducing Aβ fibril formation and exhibiting therapeutic potential.
  • Probes effectively photooxygenated Aβ, blocked ROS-mediated apoptosis, chelated Fe(III) ions, and showed good cellular uptake.
  • The developed probes mitigated metal-induced aggregation and oxidative stress, confirming their theranostic capabilities for AD.

Conclusions:

  • The developed fluorescent probes exhibit multipotent activity, offering improved early detection and a potential therapeutic strategy for slowing AD progression.
  • This research paves the way for creating multifunctional molecules as comprehensive diagnostic and therapeutic tools for neurodegenerative disorders.