Peptide based therapy for neurological disorders

: Peptides are small molecules composed of amino acids linked together by peptide bonds. The targeted action of these peptides along with their magnificent ability to reach locations in body that are complicated to access, is being considered of tremendous potential in disease modifying therapies. Synthetic as well as natural peptides like Carnosine are currently under research for treatment of neurodegenerative disorders (NDDs). Peptide based vaccines are currently under immense research for diseases like dementia. Toxicity of peptide-based drugs tfigureowards eukaryotic cells due to their increased haemolytic activity is of major concern and this is being tackled by introducing modifications into the peptide structure. Some crucial peptide inhibitors currently in use for neurodegenerative disorders include Aβ (16-20) KLVFF for Alzheimer’s disease, NAPVSIPQ (NAP) for Parkinson’s disease, towards eukaryotic cells Vasoactive Intestinal Peptides (VIP) for Huntington’s disease, Polyglutamine Binding Peptide-1(QBP1) for Dentatorubral-paiidoluysial atrophy (DRPLA). Certain peptides are involved in inhibition of mitochondrial permeability transition (MPT) that plays a prominent part in the materialization of neurodegenerative diseases, one such example of peptides being Ba-V which is obtained from Bothrops atrox snake venom. New therapeutic peptides are being identified using bioinformatics tools like high throughput screening (HTS). These tools are being used to explore the selectivity, stability, extent of immune response and toxic side effects of peptides. Apart from neurodegenerative diseases, the potential of bioactive peptides is also being tested against cancer, diabetes and microbes. This review focuses on the recent advances in peptide therapeutics and novel peptides discovered for treatment of the NDs.

Relationship between serum levels of VIP, but not of CGRP, and cranial autonomic parasympathetic symptoms: A study in chronic migraine patients

Background Cranial autonomic parasympathetic symptoms (CAPS) appear in at least half of migraine patients theoretically as a result of the release of peptides by the trigemino-vascular system (TVS). Cranial pain pathways become sensitised by repeated episodes of TVS activation, leading to migraine chronification. Objective The objective of this article is to correlate the presence of CAPS with serum levels of vasoactive intestinal peptides (VIP) and calcitonin gene-related peptide (CGRP). Patients and methods Patients with chronic migraine (CM) were asked about the presence – during migraine attacks – of five CAPS, which were scored from 0 to 10 by using a quantitative scale. Serum VIP and CGRP levels were determined by ELISA. Results We interviewed 87 CM patients (82 females; mean age 44.7 ± 10.6 years). Seventeen had no CAPS, while 70 reported at least one CAPS. VIP levels ranged from 20.8 to 668.2 pg/ml (mean 154.5 ± 123.2). There was a significant positive correlation between scores in the CAPS scale and VIP levels (Spearman correlation coefficient = 0.227; p = 0.035). VIP levels were significantly higher in CM patients by at least one point in the scale vs those with 0 points ( p = 0.002). Analysing symptoms individually, VIP levels were numerically higher in those patients with symptoms, though they were significantly higher only in those patients with lacrimation vs those without it ( p = 0.013). There was no significant correlation between CGRP levels and the score in the CAPS scale. Conclusions Serum VIP, but not CGRP, levels seem to reflect the rate of activation of the parasympathetic arm of the TVS in migraine.

Receptor binding of guinea pig and pig vasoactive intestinal peptides by rat lung

Guinea pig vasoactive intestinal peptide (gpVIP) differs from other mammalian VIPs in four of its 28 amino acid residues. In the present study, the gpVIP displaced 125I-labelled pig VIP (pVIP) binding by rat lung membranes with 7.7-fold lower potency than pVIP. Degradation of gpVIP by rat lung membranes, assessed by radioimmunoassay and h.p.l.c., was 1.9-fold greater than that of pVIP. This difference in degradation of the two peptides was not large enough to account for the lower receptor-binding potency of gpVIP. The amino acid residues that distinguish pVIP from gpVIP are likely to contribute to the interaction of VIP with receptors and peptide hydrolases in lung membranes.