{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T09:51:18Z","timestamp":1792489878845,"version":"4.5.0"},"reference-count":143,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2020,11,16]],"date-time":"2020-11-16T00:00:00Z","timestamp":1605484800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca Corrente 2020"],"award-info":[{"award-number":["Ricerca Corrente 2020"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Locus Coeruleus (LC) is the main noradrenergic nucleus of the central nervous system, and its neurons widely innervate the whole brain. LC is severely degenerated both in Alzheimer\u2019s disease (AD) and in Parkinson\u2019s disease (PD), years before the onset of clinical symptoms, through mechanisms that differ among the two disorders. Several experimental studies have shown that noradrenaline modulates neuroinflammation, mainly by acting on microglia\/astrocytes function. In the present review, after a brief introduction on the anatomy and physiology of LC, we provide an overview of experimental data supporting a pathogenetic role of LC degeneration in AD and PD. Then, we describe in detail experimental data, obtained in vitro and in vivo in animal models, which support a potential role of neuroinflammation in such a link, and the specific molecules (i.e., released cytokines, glial receptors, including pattern recognition receptors and others) whose expression is altered by LC degeneration and might play a key role in AD\/PD pathogenesis. New imaging and biochemical tools have recently been developed in humans to estimate in vivo the integrity of LC, the degree of neuroinflammation, and pathology AD\/PD biomarkers; it is auspicable that these will allow in the near future to test the existence of a link between LC-neuroinflammation and neurodegeneration directly in patients.<\/jats:p>","DOI":"10.3390\/ijms21228630","type":"journal-article","created":{"date-parts":[[2020,11,16]],"date-time":"2020-11-16T21:48:52Z","timestamp":1605563332000},"page":"8630","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Locus Coeruleus Modulates Neuroinflammation in Parkinsonism and Dementia"],"prefix":"10.3390","volume":"21","author":[{"given":"Filippo Sean","family":"Giorgi","sequence":"first","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy"},{"name":"Neurology Unit, Pisa University Hospital, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3566-4889","authenticated-orcid":false,"given":"Francesca","family":"Biagioni","sequence":"additional","affiliation":[{"name":"I.R.C.C.S. Neuromed, Via Atinense 18, 86077 Pozzilli (IS), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Galgani","sequence":"additional","affiliation":[{"name":"Neurology Unit, Pisa University Hospital, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Pavese","sequence":"additional","affiliation":[{"name":"Clinical Ageing Research Unit, Newcastle University, Newcastle upon Tyne NE4 5PL, UK"},{"name":"Institute of Clinical Medicine, PET Centre, Aarhus University, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Lazzeri","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Fornai","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy"},{"name":"I.R.C.C.S. Neuromed, Via Atinense 18, 86077 Pozzilli (IS), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1002\/glia.23571","article-title":"Neuroinflammation in the central nervous system: Symphony of glial cells","volume":"67","author":"Yang","year":"2019","journal-title":"Glia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1146\/annurev-immunol-051116-052358","article-title":"Microglia function in the central nervous system during health and neurodegeneration","volume":"35","author":"Colonna","year":"2017","journal-title":"Annu. Rev. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Pawate, S., and Bhat, N.R. (2008). Role of Glia in CNS Inflammation. 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