Date of Award

2022-05-01

Degree Name

Doctor of Philosophy

Department

Chemistry

Advisor(s)

Mahesh Narayan

Abstract

Neurodegenerative diseases such as Parkinson's disease (PD), Alzheimerâ??s Disease (AD) and Huntingtonâ??s Disease (HD) have no cure despite intensive research efforts geared towards therapeutics development. In the USA, patients with PD and AD alone cost the nation ~ $200 billion annually in patient care and lost productivity. Therefore, there remains an urgent and unmet need to develop novel drugs and drug carriers with the potential to slow down, halt and ideally reverse the course of neurodegenerative disorders. The dissertation focuses on developing approaches towards targeting PD using multifactorial mechanisms including the targeting of protein aggregation and oxidative stress. This is important because previous reports have revealed that protein aggregation and oxidative stress interact and intensify each other's effect in PD, ultimately resulting in neuronal death. A section of the dissertation underscores overcoming solubility and bioavailability limitations associated with ellagic acid (EA), a polyphenol with excellent antioxidant potential, using chitosan (CS) nanoparticles as nanocarriers. Our results reveal that encapsulation of EA in CS-based nano-ensembles results in mitigation of the PD-associated toxic effects and furthermore, overcomes solubility-related issues of the parent drug. In continuing with this theme, effort is drawn towards developing carbon quantum dots as inhibitors of amyloid fibrillation and as antioxidants. We showcase the development of a "one-pot" drug which also intervenes across multiple disease outputs. This facet is becoming increasingly important as diseases are being recognized as not being monogenic in nature but instead as progressing via a plethora of molecular aberrations that are sporadic/idiopathic. Finally, we advance analytical tools that promote a facile and cost-effective method to address the soluble-to-toxic transformation of amyloidogenic proteins. The methodological inroad is rapid, inexpensive, and quantitative and diminishes existing barriers associated with techniques to evaluate fibril formation and intervention.

Language

en

Provenance

Recieved from ProQuest

File Size

127 p.

File Format

application/pdf

Rights Holder

Jyoti Ahlawat

Share

COinS