Potentials of Neuropeptides as Therapeutic Agents for Neurological Diseases

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.

Comprehensive Review on Potential Signaling Pathways Involving the Transfer of α-Synuclein from the Gut to the Brain That Leads to Parkinson’s Disease

“…Toxins produced by microbes in the gut have been proposed to play a key role in the pathogenesis of PD by inducing the production of α-syn aggregates in the ENS, which then spread in a prion-like fashion through the vagus nerve to the CNS. Systemic inflammation could be encouraged by an overactive innate immune system caused by intestine bacterial overgrowth or gut dysbiosis, and the activation of enteric glial cells and enteric neurons could contribute to α-synucleinopathy. , The signaling molecules neuropeptide Y (NpY), cholecytokinin (CCK), ghrelin, and leptin, as well as neurotransmitters and glutamate, are thought to be the primary means of communication through GABA. , Neurotransmitter levels are reduced in PD . Microbiome-derived metabolites, or microbial metabolites, are small molecules that have been shown to affect host neurophysiology in various ways.…”

Alternative Pharmacological Strategies for the Treatment of Alzheimer’s Disease: Focus on Neuromodulator Function

“…Upon release from neurons, they act locally or over long distances, and are able to exert a vast array of very fast (milliseconds) or long-lasting (seconds to minutes) effects on autocrine and paracrine targets [ 88 ]. Interactions between neuropeptides and neurotransmitters, alongside their independent activities, are vital for the modulation of neuronal activity associated with neurodevelopment, neuronal homeostasis, sensory perception, the inflammatory response and metabolic function [ 89 ]. Critically, neuropeptide binding to G-protein-coupled receptors (GPCRs) in the hippocampus is able to activate numerous signalling pathways in order to modulate synaptic plasticity.…”

“…Due to a lack of reuptake mechanisms, neuropeptides tend to exert longer-lasting effects on relevant targets from large distances. This is difficult to achieve with neurotransmitter targeting, which is predominantly faster acting with rapid reuptake [ 89 ]. Neuropeptide targeting may therefore enable effects to reach a more substantial target area, without the requirement for frequent dosing.…”

Characterization of Hippocampal Synaptic Plasticity in Orchidectomized Insulin-resistant Rats

“…Synaptic plasticity is also thought to play key roles in the early development of neural circuitry. In fact impairments in synaptic plasticity mechanisms contribute to several prominent neuropsychiatric disorders (Alibhai, 2010;Liu, 2011;Kuwahara, 2021;Yeo, 2022).…”