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Exploring the Role of Orexinergic Neurons in Parkinson's Disease

Journal

NEUROTOXICITY RESEARCH
Volume 39, Issue 6, Pages 2141-2153

Publisher

SPRINGER
DOI: 10.1007/s12640-021-00411-4

Keywords

Orexinergic system; Parkinson's disease; Orexin; Hypocretin; Narcolepsy; Neuroprotection

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This study reviewed the changes in the orexinergic system in parkinsonian subjects and found dysfunctioning of this system to be linked with non-motor symptoms (sleep abnormalities) in PD. Orexinergic neurons' behavior is modulated by various factors, and orexin antagonists have been shown to improve abnormal sleep patterns. Since the orexinergic system plays a role in several psychological and neurological disorders, targeting this system could potentially help manage these disorders.
Parkinson's disease (PD) is a neurodegenerative disease affecting about 2% of the population. A neuropeptide, orexin, is linked with sleep abnormalities in the parkinsonian patient. This study aimed to review the changes in the orexinergic system in parkinsonian subjects and the effects of orexin. A number of search techniques were used and presumed during the search, including cloud databank searches of PubMed and Medline using title words, keywords, and MeSH terms. PD is characterised by motor dysfunctions (postural instability, rigidity, tremor) and cognitive disorders, sleep-wake abnormalities grouped under non-motor disorders. The Orexinergic system found in the hypothalamus is linked with autonomic function, neuroprotection, learning and memory, and the sleep-wake cycle. Prepro-orexin, a precursor peptide (130 amino acids), gives rise to orexins (Orx-A and Orx-B). Serum orexin level measurement is vital for evaluating several neurological disorders (Alzheimer's disease, Huntington's disease, and PD). Orexinergic neurons are activated by hypoglycemia and ghrelin, while they are restrained by food consumption and leptin. Orexinergic system dysfunctioning was found to be linked with non-motor symptoms (sleep abnormalities) in PD. Orexinergic neuron's behaviour may be either inhibitory or excitatory depending on the environment in which they are present. As well, orexin antagonists are found to improve the abnormal sleep pattern. Since the orexinergic system plays a role in several psychological and neurological disorders, therefore, these disorders can be managed by targeting this system.

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