000169044 001__ 169044 000169044 005__ 20250127111029.0 000169044 0247_ $$2ISSN$$a1545-5343 000169044 0247_ $$2pmc$$apmc:PMC10119350 000169044 0247_ $$2doi$$a10.1007/s13311-022-01332-6 000169044 0247_ $$2pmid$$apmid:36512255 000169044 0247_ $$2ISSN$$a1933-7213 000169044 0247_ $$2ISSN$$a1878-7479 000169044 0247_ $$2altmetric$$aaltmetric:140247020 000169044 0247_ $$2ISSN$$a1545-5351 000169044 037__ $$aDZNE-2022-01766 000169044 041__ $$aEnglish 000169044 082__ $$a610 000169044 1001_ $$0P:(DE-2719)9001609$$aPinto-Costa, Rita$$b0$$eFirst author$$udzne 000169044 245__ $$aOverexpression-Induced α-Synuclein Brain Spreading. 000169044 260__ $$aNew York, NY$$bSpringer$$c2023 000169044 3367_ $$2DRIVER$$aarticle 000169044 3367_ $$2DataCite$$aOutput Types/Journal article 000169044 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1683032127_12618$$xReview Article 000169044 3367_ $$2BibTeX$$aARTICLE 000169044 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000169044 3367_ $$00$$2EndNote$$aJournal Article 000169044 520__ $$aInterneuronal transfer of pathological α-synuclein species is thought to play an important role in the progressive advancement of Lewy pathology and increasing severity of clinical manifestations in Parkinson's and other diseases commonly referred to as synucleinopathies. Pathophysiological conditions and mechanisms triggering this trans-synaptic spreading bear therefore significant pathogenetic implications but have yet to be fully elucidated. In vivo experimental models support the conclusion that increased expression of intraneuronal α-synuclein can itself induce protein spreading throughout the brain as well as from the brain to peripheral tissues. For example, overexpression of α-synuclein targeted to the rodent dorsal medulla oblongata results in its transfer and accumulation into recipient axons innervating this brain region; through these axons, α-synuclein can then travel caudo-rostrally and reach other brain sites in the pons, midbrain, and forebrain. When protein overexpression is induced in the rodent midbrain, long-distance α-synuclein spreading can be followed over time; spreading-induced α-synuclein accumulation affects lower brain regions, including the dorsal motor nucleus of the vagus, proceeds through efferent axons of the vagus nerve, and is ultimately detected within vagal motor nerve endings in the gastric wall. As discussed in this review, animal models featuring α-synuclein overexpression not only support a relationship between α-synuclein burden and protein spreading but have also provided important clues on conditions/mechanisms capable of promoting interneuronal α-synuclein transfer. Intriguing findings include the relationship between neuronal activity and protein spreading and the role of oxidant stress in trans-synaptic α-synuclein mobility. 000169044 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0 000169044 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de 000169044 650_2 $$2MeSH$$aAnimals 000169044 650_2 $$2MeSH$$aalpha-Synuclein: metabolism 000169044 650_2 $$2MeSH$$aBrain: metabolism 000169044 650_2 $$2MeSH$$aNeurons: metabolism 000169044 650_2 $$2MeSH$$aParkinson Disease: metabolism 000169044 650_2 $$2MeSH$$aStomach: innervation 000169044 650_2 $$2MeSH$$aStomach: metabolism 000169044 650_2 $$2MeSH$$aSynaptic Transmission: physiology 000169044 650_2 $$2MeSH$$aSynucleinopathies: metabolism 000169044 650_2 $$2MeSH$$aVagus Nerve: metabolism 000169044 650_2 $$2MeSH$$aVagus Nerve: physiology 000169044 650_7 $$2NLM Chemicals$$aalpha-Synuclein 000169044 650_7 $$2Other$$aAnimal models 000169044 650_7 $$2Other$$aGut-brain axis 000169044 650_7 $$2Other$$aNeuronal activity 000169044 650_7 $$2Other$$aOxidative stress 000169044 650_7 $$2Other$$aParkinson 000169044 650_7 $$2Other$$aVagus nerve 000169044 7001_ $$0P:(DE-2719)9001593$$aHarbachova, Eugenia$$b1$$udzne 000169044 7001_ $$0P:(DE-2719)9001592$$aLa Vitola, Pietro$$b2$$udzne 000169044 7001_ $$0P:(DE-2719)2481741$$aDi Monte, Donato Antonio$$b3$$eLast author$$udzne 000169044 773__ $$0PERI:(DE-600)2279496-7$$a10.1007/s13311-022-01332-6$$n1$$p83-96$$tNeurotherapeutics$$v20$$x1933-7213$$y2023 000169044 8564_ $$uhttps://pub.dzne.de/record/169044/files/DZNE-2022-01766.pdf$$yOpenAccess 000169044 8564_ $$uhttps://pub.dzne.de/record/169044/files/DZNE-2022-01766.pdf?subformat=pdfa$$xpdfa$$yOpenAccess 000169044 909CO $$ooai:pub.dzne.de:169044$$pdnbdelivery$$pdriver$$pVDB$$popen_access$$popenaire 000169044 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9001609$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b0$$kDZNE 000169044 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9001593$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b1$$kDZNE 000169044 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9001592$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b2$$kDZNE 000169044 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2481741$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b3$$kDZNE 000169044 9131_ $$0G:(DE-HGF)POF4-352$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vDisease Mechanisms$$x0 000169044 9141_ $$y2022 000169044 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2022-11-08 000169044 915__ $$0LIC:(DE-HGF)CCBY4$$2HGFVOC$$aCreative Commons Attribution CC BY 4.0 000169044 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2022-11-08 000169044 915__ $$0StatID:(DE-HGF)3002$$2StatID$$aDEAL Springer$$d2022-11-08$$wger 000169044 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess 000169044 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2023-10-25 000169044 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central$$d2023-10-25 000169044 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2023-10-25 000169044 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2023-10-25 000169044 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2023-10-25 000169044 915__ $$0StatID:(DE-HGF)1110$$2StatID$$aDBCoverage$$bCurrent Contents - Clinical Medicine$$d2023-10-25 000169044 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bNEUROTHERAPEUTICS : 2022$$d2023-10-25 000169044 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2023-10-25 000169044 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bNEUROTHERAPEUTICS : 2022$$d2023-10-25 000169044 9201_ $$0I:(DE-2719)1013008$$kAG Di Monte$$lNeurodegeneration and Neuroprotection in Parkinson´s Disease$$x0 000169044 980__ $$ajournal 000169044 980__ $$aVDB 000169044 980__ $$aI:(DE-2719)1013008 000169044 980__ $$aUNRESTRICTED 000169044 9801_ $$aFullTexts