H ₂ S-releasing peptide frameworks: a multifaceted therapeutic approach to Alzheimer's disease Rafat Ali 1 , Rohil Hameed 2 , Divya Chauhan 3 , Shantanu Sen 1 , Muhammad Wahajuddin 3 , Aamir Nazir 2 , Sandeep Verma 1,4, 1 Department of Chemistry, Indian Institute of Technology Kanpur, India, 2 Division of Neuroscience and Ageing Biology, CSIR-Central Drug Research Institute,India, Academy of Scientific and Innovative Research (AcSIR),India, 3 Division of Pharmaceutics & Pharmacokinetics, CSIR- Central Drug Research Institute, India; Academy of Scientific and Innovative Research (AcSIR), India, 4 Centre for Nanoscience and Mehta Family Center for Engineering in Medicine, Indian Institute of Technology Kanpur, India Alzheimer's disease (AD) is a debilitating and progressive neurodegenerative disorder that causes cognitive decline. Its complex nature, associated with factors such as Aβ plaque deposition, oxidative stress, neuronal cell inflammation, and low levels of the neurotransmitter acetylcholine (ACh), presents a significant obstacle to developing a complete cure. Current therapies only alleviate symptoms without addressing the underlying causes or disease progression. Therefore, there is a pressing need for new therapeutic approaches that can target disease-causing pathways rather than just offering symptomatic relief. Hydrogen sulfide (H2S), once regarded as a toxic gas, is now recognized as an endogenous signaling molecule with antioxidant, neuroprotective, and neuromodulatory properties. But the therapeutic potential of H2S depends on its duration of release and local concentration. We have successfully designed and synthesized peptide frameworks that release H2S in a slow and controlled manner. These peptides form distinct nanostructures in aqueous solutions and deliver H2S effectively within Caenorhabditis elegans (C. elegans). These peptide conjugates target multiple factors responsible for AD progression, including reducing oxidative stress, inhibiting Aβ aggregation, and increasing ACh levels in a transgenic C. elegans model expressing human Aβ.
References 1. Ali, Rafat; Hameed, Rohil; Chauhan, Divya; Sen, Shantanu; Wahajuddin, Muhammad; Nazir, Aamir; Verma, Sandeep. Multiple Actions of H 2 S-Releasing Peptides in Human β-Amyloid ExpressingC. elegans ACS Chemical Neuroscience 2022 , 13 , 3378-3388 2. Ali, Rafat; Pal, Hilal Ahmad; Hameed, Rohil; Nazir, Aamir; Verma, Sandeep. Controlled release of hydrogen sulfide significantly reduces ROS stress and increases dopamine levels in transgenic C. elegans. Chemical Communications2019 , 55 , 10142-10145.
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