The novel role of the neuropeptides orexin and QRFP and their involvement in Alzheimer's disease
Year: 2014
Type: dissertation
Abstract: Alzheimer's disease (AD) is a neurodegenerative disease which affects over 500,000 people in the UK.Worldwide 44 million people are affected by AD and other dementias.Most cases occur over the age of 65 and is characterised by gradual and increasing loss of cognitive function and behavioural abnormalities.The main causes are a build-up of the toxic protein amyloid-β (Aβ) and hyperphosphorylation of the microtubule stabilising protein: tau, leading to neurofibrillary tangles (NFT).These two hallmarks of disease result in neuronal damage and cell death causing associated symptoms and eventually death.Orexins (OX) are neuropeptides which function to regulate the sleep-wake cycle and feeding behaviour.They are produced from a prepro-orexin (PPO) molecule and cleaved into two isoforms: orexin-A (OXA) and orexin-B (OXB).OXA and OXB are the ligands for two G-protein coupled receptors (GPCR): orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R).50-80,000 OX producing neurons project to many areas of the brain including the lateral hypothalamus (LHA), locus coeruleus (LC), tuberomammillary nucleus (TMN), paraventricular nucleus (PVN) and raphe nuclei and from these areas regulate feeding and appetite and the sleep wake cycle through their receptors.QRFP is a newly discovered neuropeptide which exerts similar orexigenic activity including the control of feeding behaviour.It is the ligand for the GPCR GPR103, both of which are widely expressed in the brain and also in the retina, testes, thyroid, pituitary and prostate.GPR103 also shares 48 and 47% protein sequence homology with OX1R and OX2R respectively.It is in these tissues List of abbreviations ACEAngiotensin-converting enzyme LOAD Late-onset Alzheimer's disease dNTP Deoxyribonucleotide LRP1 Low density lipoprotein receptor-related protein 1 8-OHG 8-hydroxydeoxyguanosine MAPK Mitogen-activated protein kinase ACh Acetylcholine MAPK14 Mitogen-activated protein kinase 14 AChE1 Acetylcholinesterase MAPT Microtubule
Author: Julie Davies
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W114463656