neuropeptide-y and Amyotrophic-Lateral-Sclerosis

Neuropeptide Y (NPY) is an endogenous peptide of the central and enteric nervous systems which has gained significant interest as a potential neuroprotective agent for treatment of neurodegenerative disease. Amyotrophic lateral sclerosis (ALS) is an aggressive and fatal neurodegenerative disease characterized by motor deficits and motor neuron loss. In ALS, recent evidence from ALS patients and animal models has indicated that NPY may have a role in the disease pathogenesis. Increased NPY levels were found to correlate with disease progression in ALS patients. Similarly, NPY expression is increased in the motor cortex of ALS mice by end stages of the disease. Although the functional consequence of increased NPY levels in ALS is currently unknown, NPY has been shown to exert a diverse range of neuroprotective roles in other neurodegenerative diseases; through modulation of potassium channel activity, increased production of neurotrophins, inhibition of endoplasmic reticulum stress and autophagy, reduction of excitotoxicity, oxidative stress, neuroinflammation and hyperexcitability. Several of these mechanisms and signalling pathways are heavily implicated in the pathogenesis of ALS. Therefore, in this review, we discuss possible effects of NPY and NPY-receptor signalling in the ALS disease context, as determining NPY's contribution to, or impact on, ALS disease mechanisms will be essential for future studies investigating the NPY system as a therapeutic strategy in this devastating disease.

Topics: Amyotrophic Lateral Sclerosis; Animals; Humans; Neuropeptide Y; Receptors, Neuropeptide Y

Physiological changes potentially influence disease progression and survival along the Amyotrophic Lateral Sclerosis (ALS)-Frontotemporal dementia (FTD) spectrum. The peripheral peptides that regulate eating and metabolism may provide diagnostic, metabolic, and progression biomarkers. The current study aimed to examine the relationships and biomarker potential of hormonal peptides.. One hundred and twenty-seven participants (36 ALS, 26 ALS- cognitive, patients with additional cognitive behavioral features, and 35 behavioral variant FTD (bvFTD) and 30 controls) underwent fasting blood analyses of leptin, ghrelin, neuropeptide Y (NPY), peptide YY (PYY), and insulin levels. Relationships between endocrine measures, cognition, eating behaviors, and body mass index (BMI) were investigated. Biomarker potential was evaluated using multinomial logistic regression for diagnosis and correlation to disease duration.. Compared to controls, ALS and ALS-cognitive had higher NPY levels and bvFTD had lower NPY levels, while leptin levels were increased in all patient groups. All groups had increased insulin levels and a state of insulin resistance compared to controls. Lower NPY levels correlated with increasing eating behavioral change and BMI, while leptin levels correlated with BMI. On multinomial logistic regression, NPY and leptin levels were found to differentiate between diagnosis. Reduced Neuropeptide Y levels correlated with increasing disease duration, suggesting it may be useful as a potential marker of disease progression.. ALS-FTD is characterized by changes in NPY and leptin levels that may impact on the underlying regional neurodegeneration as they were predictive of diagnosis and disease duration, offering the potential as biomarkers and for the development of interventional treatments.

Topics: Amyotrophic Lateral Sclerosis; Biomarkers; Disease Progression; Fasting; Feeding Behavior; Female; Frontotemporal Dementia; Ghrelin; Humans; Insulin; Leptin; Male; Middle Aged; Neuropeptide Y; Neuropeptides; Peptide YY; Predictive Value of Tests

Increasing evidence indicates an excitatory/inhibitory imbalance may have a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS). Impaired inhibitory circuitry is consistently reported in the motor cortex of both familial and sporadic patients, closely associated with cortical hyperexcitability and ALS onset. Inhibitory network dysfunction is presumably mediated by intra-cortical inhibitory interneurons, however, the exact cell types responsible are yet to be identified. In this study we demonstrate dynamic changes in the number of calretinin- (CR) and neuropeptide Y-expressing (NPY) interneurons in the motor cortex of the familial hSOD1

Topics: Amyotrophic Lateral Sclerosis; Animals; Calbindin 2; Disease Models, Animal; Humans; Interneurons; Mice; Mice, Transgenic; Motor Cortex; Motor Neurons; Mutation; Neuropeptide Y; Superoxide Dismutase-1

We performed a quantitative histochemical study of neuropeptide Y (NPY) immunoreactivity in postmortem human brain to further define patterns of neuronal degeneration in amyotrophic lateral sclerosis (ALS). The density of NPY fibers was decreased in ALS motor cortex but not in other cortical regions or striatum. Although, the density of cortical NPY neurons was unchanged in high grade cases, neurons were shrunken and atrophic with pruned dendrites. NPY neurons are less severely affected than parvalbumin neurons which are severely depleted in ALS cortex. This differential involvement of local circuit neurons suggests that a simple excitotoxic model may not adequately explain patterns of neuronal loss in ALS.

Topics: Adult; Aged; Amyotrophic Lateral Sclerosis; Cerebral Cortex; Dendrites; Female; Humans; Immunohistochemistry; Male; Middle Aged; Motor Cortex; Motor Neurons; Neurons; Neuropeptide Y