Context:

A team of scientists at the Indian Association for the Cultivation of Science (IASST), an autonomous institute of the Department of Science and Technology (DST), has been exploring peptidomimetics, synthetic compounds designed to mimic neurotrophins, as a potential solution to these limitations.

About the research:

Led by Prof. Ashis K. Mukherjee, the IASST researchers have conducted extensive studies on neurotrophin peptidomimetics. Their research, published in the Journal Drug Discovery Today focused on understanding the signaling pathways involved in neuronal growth and survival, the potential pharmacological targets of peptidomimetics, and their therapeutic applications for NDs.

About Neurodegenerative diseases :

Neurodegenerative diseases are a group of disorders characterized by the progressive loss of structure or function of neurons (nerve cells) in the brain and nervous system. Common examples include:

·         Alzheimer’s disease

·         Parkinson’s disease

·         Huntington’s disease

·         Amyotrophic lateral sclerosis (ALS)

About neurotrophins:

Neurotrophins are a family of proteins essential for:

• Promoting neuronal growth
• Supporting neuronal survival
• Facilitating synaptic plasticity (key for memory and learning)

Despite their therapeutic potential, natural neurotrophins are unstable, degrade quickly in the body, and have poor brain penetration—limiting their clinical use.

About peptidomimetics:

Peptidomimetics are synthetic molecules designed to mimic the structure and biological function of natural peptides or proteins, such as neurotrophins. They are engineered to overcome key limitations of natural peptides, including:

• Poor oral bioavailability
• Short half-life
• Degradation by enzymes

These synthetic compounds:

• Bind to neurotrophin receptors on neurons
• Activate signaling pathways that promote cell survival, growth, and repair
• Mimic the action of natural neurotrophins without the drawbacks of instability or immune reactions

Advantage of using neurotrophin peptidomimetics in treating NDs

Key advantages include:

• Improved stability in the bloodstream
• Enhanced brain permeability
• Longer duration of action
• Reduced immunogenicity (less likely to trigger immune responses)
• Target specificity, lowering the risk of off-target side effects

What has the research found so far?

• The peptidomimetics show promising effects on neuronal survival and regeneration.
• The team has identified potential signaling pathways and pharmacological targets.
• There is potential to repurpose existing peptidomimetic drugs for use in NDs and other conditions like cancer.

Future implication:

If successful, neurotrophin peptidomimetics could:

• Become a mainstream therapeutic strategy for neurodegenerative diseases
• Be custom-designed for specific diseases or patient populations
• Offer new hope for slowing or halting disease progression