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However, less is known about the role of orexigenic neuropeptides\u2014including neuropeptide Y, agouti-related peptide, melanin-concentrating hormone, orexins, galanin, and peripherally released hormone ghrelin\u2014that are best known for their role in energy balance and stimulation of food intake. Growing evidence highlights their broader neuroprotective properties across preclinical models of Alzheimer\u2019s disease (AD) and Parkinson\u2019s disease (PD). In AD, these peptides reduce hallmark pathologies such as amyloid burden, tau phosphorylation, oxidative stress, and neuroinflammation, while enhancing synaptogenesis, neurogenesis, and cognitive function. In PD models, ghrelin protects nigrostriatal dopaminergic neurons by restoring autophagic flux, suppressing endoplasmic reticulum stress-mediated apoptosis, and reducing microglial activation, whereas orexin A and B preserve tyrosine hydroxylase expression, promote neuronal excitability, and improve motor and cognitive outcomes. Taken together, these findings position orexigenic peptides as promising modulators of neurodegeneration and highlight their potential as therapeutic targets in AD and PD.<\/jats:p>","DOI":"10.1042\/bsr20250362","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T08:29:03Z","timestamp":1777624143000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative role of orexigenic peptides in neuroprotection and neurodegenerative disease modulation"],"prefix":"10.1042","volume":"46","author":[{"given":"Zuzana","family":"Sopko","sequence":"first","affiliation":[{"name":"Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, 16610 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Pa\u010desov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, 16610 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blanka","family":"\u017delezn\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, 16610 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4299-8983","authenticated-orcid":false,"given":"Lenka","family":"Malet\u00ednsk\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, 16610 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"2026062905470126100_B1","doi-asserted-by":"publisher","first-page":"BSR20231385","DOI":"10.1042\/BSR20231385","article-title":"Anorexigenic neuropeptides as anti-obesity and neuroprotective agents","volume":"44","author":"Strnadov\u00e1","year":"2024","journal-title":"Biosci. 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