Abstract
Despite recent leaps in modern medicine, progress in the treatment of neurological diseases remains slow. The near impermeable blood-brain barrier (BBB) that prevents the entry of therapeutics into the brain, and the complexity of neurological processes, limits the specificity of potential therapeutics. Moreover, a lack of etiological understanding and the irreversible nature of neurological conditions have resulted in low tolerability and high failure rates towards existing small molecule-based treatments. Neuropeptides, which are small proteinaceous molecules produced by the body, either in the nervous system or the peripheral organs, modulate neurological function. Although peptide-based therapeutics originated from the treatment of metabolic diseases in the 1920s, the adoption and development of peptide drugs for neurological conditions are relatively recent. In this review, we examine the natural roles of neuropeptides in the modulation of neurological function and the development of neurological disorders. Furthermore, we highlight the potential of these proteinaceous molecules in filling gaps in current therapeutics.
Highlights
The accelerated acquisition of scientific knowledge and development of modern medicine have resulted in numerous miracles over the past 20 years
Similar to Vasoactive intestinal peptide (VIP), polymorphisms in the OXTR gene encoding the oxytocin receptor have been linked to the development of autism spectrum disorder (ASD) [61,63,64,65], a further reflection of the neuropeptide’s role in neurodevelopmental processes
At an early stage of brain development, neuropeptides regulate synapse formation and neuronal proliferation and differentiation. They have been shown to modulate ion channel activity, neurotransmitter release, and synaptic plasticity, all of which contribute to maintaining the excitatory and inhibitory (E/I) balance within the brain
Summary
The accelerated acquisition of scientific knowledge and development of modern medicine have resulted in numerous miracles over the past 20 years. Small peptide drugs provide an alternate avenue for the development of novel therapeutics targeting neurological conditions. Neuropeptides are small endogenous protein messengers synthesized and secreted by neurons through the regulated secretory route [37] They are produced widely in the nervous system as pro-peptides, which are further cleaved into smaller fragments, commonly between 5 and 80 amino acids, through a multistep process. The neuropeptide family comprises a broad range of proteinaceous molecules with known pleiotropic effects in development, reproduction, physiology, and behaviour [41,42,43] They can act as hormones, neurotransmitters, and neuromodulators in the nervous system. They are good candidates for novel drug development for various neurological conditions. For more detailed discussions of the topics presented, we encourage readers to refer to review papers pointed to in the text
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