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000272487 0247_ $$2doi$$a10.1016/j.neuron.2024.06.029
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000272487 041__ $$aEnglish
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000272487 1001_ $$0P:(DE-2719)9000371$$aScheiblich, Hannah$$b0$$eFirst author
000272487 245__ $$aMicroglia rescue neurons from aggregate-induced neuronal dysfunction and death through tunneling nanotubes.
000272487 260__ $$aNew York, NY$$bElsevier$$c2024
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000272487 520__ $$aMicroglia are crucial for maintaining brain health and neuron function. Here, we report that microglia establish connections with neurons using tunneling nanotubes (TNTs) in both physiological and pathological conditions. These TNTs facilitate the rapid exchange of organelles, vesicles, and proteins. In neurodegenerative diseases like Parkinson's and Alzheimer's disease, toxic aggregates of alpha-synuclein (α-syn) and tau accumulate within neurons. Our research demonstrates that microglia use TNTs to extract neurons from these aggregates, restoring neuronal health. Additionally, microglia share their healthy mitochondria with burdened neurons, reducing oxidative stress and normalizing gene expression. Disrupting mitochondrial function with antimycin A before TNT formation eliminates this neuroprotection. Moreover, co-culturing neurons with microglia and promoting TNT formation rescues suppressed neuronal activity caused by α-syn or tau aggregates. Notably, TNT-mediated aggregate transfer is compromised in microglia carrying Lrrk22(Gly2019Ser) or Trem2(T66M) and (R47H) mutations, suggesting a role in the pathology of these gene variants in neurodegenerative diseases.
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000272487 650_7 $$2Other$$aLrrk2 G2019S
000272487 650_7 $$2Other$$aTrem2
000272487 650_7 $$2Other$$aalpha-synuclein
000272487 650_7 $$2Other$$aintercellular transfer
000272487 650_7 $$2Other$$amicroglia
000272487 650_7 $$2Other$$amitochondria
000272487 650_7 $$2Other$$aneurons
000272487 650_7 $$2Other$$aoxidative stress
000272487 650_7 $$2Other$$atau
000272487 650_7 $$2Other$$atunneling nanotubes
000272487 650_7 $$2NLM Chemicals$$atau Proteins
000272487 650_7 $$2NLM Chemicals$$aTunneling Nanotubes
000272487 650_7 $$2NLM Chemicals$$aalpha-Synuclein
000272487 650_7 $$0EC 2.7.11.1$$2NLM Chemicals$$aLeucine-Rich Repeat Serine-Threonine Protein Kinase-2
000272487 650_2 $$2MeSH$$aMicroglia: metabolism
000272487 650_2 $$2MeSH$$aMicroglia: drug effects
000272487 650_2 $$2MeSH$$aAnimals
000272487 650_2 $$2MeSH$$aNeurons: metabolism
000272487 650_2 $$2MeSH$$aNeurons: drug effects
000272487 650_2 $$2MeSH$$atau Proteins: metabolism
000272487 650_2 $$2MeSH$$atau Proteins: genetics
000272487 650_2 $$2MeSH$$aalpha-Synuclein: metabolism
000272487 650_2 $$2MeSH$$aalpha-Synuclein: genetics
000272487 650_2 $$2MeSH$$aCoculture Techniques
000272487 650_2 $$2MeSH$$aMice
000272487 650_2 $$2MeSH$$aMitochondria: metabolism
000272487 650_2 $$2MeSH$$aMitochondria: drug effects
000272487 650_2 $$2MeSH$$aHumans
000272487 650_2 $$2MeSH$$aLeucine-Rich Repeat Serine-Threonine Protein Kinase-2: genetics
000272487 650_2 $$2MeSH$$aLeucine-Rich Repeat Serine-Threonine Protein Kinase-2: metabolism
000272487 650_2 $$2MeSH$$aCell Death: drug effects
000272487 650_2 $$2MeSH$$aCell Death: physiology
000272487 650_2 $$2MeSH$$aNanotubes
000272487 650_2 $$2MeSH$$aCells, Cultured
000272487 650_2 $$2MeSH$$aCell Communication: physiology
000272487 650_2 $$2MeSH$$aCell Communication: drug effects
000272487 650_2 $$2MeSH$$aOxidative Stress: drug effects
000272487 650_2 $$2MeSH$$aOxidative Stress: physiology
000272487 650_2 $$2MeSH$$aCell Membrane Structures
000272487 7001_ $$0P:(DE-2719)9002573$$aEikens, Frederik$$b1
000272487 7001_ $$0P:(DE-2719)2811527$$aWischhof, Lena$$b2$$udzne
000272487 7001_ $$aOpitz, Sabine$$b3
000272487 7001_ $$aJüngling, Kay$$b4
000272487 7001_ $$aCserép, Csaba$$b5
000272487 7001_ $$aSchmidt, Susanne V$$b6
000272487 7001_ $$aLambertz, Jessica$$b7
000272487 7001_ $$aBellande, Tracy$$b8
000272487 7001_ $$aPósfai, Balázs$$b9
000272487 7001_ $$aGeck, Charlotte$$b10
000272487 7001_ $$aSpitzer, Jasper$$b11
000272487 7001_ $$aOdainic, Alexandru$$b12
000272487 7001_ $$0P:(DE-2719)9002230$$aCastro-Gomez, Mario Sergio$$b13$$udzne
000272487 7001_ $$aSchwartz, Stephanie$$b14
000272487 7001_ $$aBoussaad, Ibrahim$$b15
000272487 7001_ $$aKrüger, Rejko$$b16
000272487 7001_ $$aGlaab, Enrico$$b17
000272487 7001_ $$0P:(DE-2719)2481741$$aDi Monte, Donato A$$b18$$udzne
000272487 7001_ $$0P:(DE-2719)2158358$$aBano, Daniele$$b19$$udzne
000272487 7001_ $$aDénes, Ádám$$b20
000272487 7001_ $$0P:(DE-2719)2000062$$aLatz, Eicke$$b21$$udzne
000272487 7001_ $$aMelki, Ronald$$b22
000272487 7001_ $$aPape, Hans-Christian$$b23
000272487 7001_ $$0P:(DE-2719)2000008$$aHeneka, Michael T$$b24$$eLast author$$udzne
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