NLP21 / NovaLead Pharma - LARVOL DELTA

IGF-like growth factors that couple food sensing to developmental decisions employ different release mechanisms in a single pair of C. elegans chemosensory neurons. (PubMed, bioRxiv) - "In addition, we find that mechanisms for delivering vesicles to the axons are also divergent: while neuropeptide NLP-21 was dependent on the clathrin adaptor AP-3 for its selective localization to axons, four insulin/IGF-like growth factors tested - DAF-28, INS-6, INS-4, and INS-22, were AP-3-independent for either axonal localization or function...These divergent vesicle pathways provide new means for the immediate and tunable changes in neuronal outputs, in addition to the known, less immediate mechanism of differential transcriptional regulation of DCV cargoes. Future delineation of the molecular composition of these pathways is necessary to understand how neurons match organismal responses to specific sensory inputs."

Journal

Loss of neuropeptidergic regulation of cholinergic transmission induces homeostatic compensation in muscle cells to preserve synaptic strength. (PubMed, PLoS Biol) - "Based on expression profiles, we identified neuropeptides involved in both cholinergic (FLP-6, FLP-15, NLP-9, NLP-15, NLP-21, and NLP-38) and GABAergic motor neurons (FLP-15, NLP-15), that mediate normal transmission at the NMJ...We show that in the absence of UNC-31 muscle excitability is modulated by upregulating the expression of the muscular L-type voltage-gated Ca2+ channel EGL-19. Our results unveil a role for neuropeptidergic regulation in synaptic plasticity, linking changes in presynaptic transmission to compensatory changes in muscle excitability."

Journal

Silica Nanoparticles Disclose a Detailed Neurodegeneration Profile throughout the Life Span of a Model Organism. (PubMed, J Xenobiot) - "Consistent with this, reporter strains for nlp-3, nlp-14 and nlp-21 confirmed premature degeneration of the serotonergic neuron HSN and other neurons in young C. elegans. The results identify young nematodes as a vulnerable age group for nano silica-induced neural defects with a significantly reduced health span. Neurodegeneration of specific neurons impairs signaling by classical neurotransmitters as well as neuropeptides and compromises related neuromuscular behaviors in critical phases of life, such as the reproductive phase."

Journal • CNS Disorders