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001     272487
005     20241001164214.0
024 7 _ |a 10.1016/j.neuron.2024.06.029
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024 7 _ |a pmid:39059388
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024 7 _ |a 0896-6273
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024 7 _ |a 1097-4199
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024 7 _ |a altmetric:165681648
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037 _ _ |a DZNE-2024-01168
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Scheiblich, Hannah
|0 P:(DE-2719)9000371
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245 _ _ |a Microglia rescue neurons from aggregate-induced neuronal dysfunction and death through tunneling nanotubes.
260 _ _ |a New York, NY
|c 2024
|b Elsevier
336 7 _ |a article
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520 _ _ |a Microglia 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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536 _ _ |a 351 - Brain Function (POF4-351)
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650 _ 7 |a Lrrk2 G2019S
|2 Other
650 _ 7 |a Trem2
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650 _ 7 |a alpha-synuclein
|2 Other
650 _ 7 |a intercellular transfer
|2 Other
650 _ 7 |a microglia
|2 Other
650 _ 7 |a mitochondria
|2 Other
650 _ 7 |a neurons
|2 Other
650 _ 7 |a oxidative stress
|2 Other
650 _ 7 |a tau
|2 Other
650 _ 7 |a tunneling nanotubes
|2 Other
650 _ 7 |a tau Proteins
|2 NLM Chemicals
650 _ 7 |a Tunneling Nanotubes
|2 NLM Chemicals
650 _ 7 |a alpha-Synuclein
|2 NLM Chemicals
650 _ 7 |a Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
|0 EC 2.7.11.1
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650 _ 2 |a Microglia: metabolism
|2 MeSH
650 _ 2 |a Microglia: drug effects
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Neurons: metabolism
|2 MeSH
650 _ 2 |a Neurons: drug effects
|2 MeSH
650 _ 2 |a tau Proteins: metabolism
|2 MeSH
650 _ 2 |a tau Proteins: genetics
|2 MeSH
650 _ 2 |a alpha-Synuclein: metabolism
|2 MeSH
650 _ 2 |a alpha-Synuclein: genetics
|2 MeSH
650 _ 2 |a Coculture Techniques
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Mitochondria: metabolism
|2 MeSH
650 _ 2 |a Mitochondria: drug effects
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Leucine-Rich Repeat Serine-Threonine Protein Kinase-2: genetics
|2 MeSH
650 _ 2 |a Leucine-Rich Repeat Serine-Threonine Protein Kinase-2: metabolism
|2 MeSH
650 _ 2 |a Cell Death: drug effects
|2 MeSH
650 _ 2 |a Cell Death: physiology
|2 MeSH
650 _ 2 |a Nanotubes
|2 MeSH
650 _ 2 |a Cells, Cultured
|2 MeSH
650 _ 2 |a Cell Communication: physiology
|2 MeSH
650 _ 2 |a Cell Communication: drug effects
|2 MeSH
650 _ 2 |a Oxidative Stress: drug effects
|2 MeSH
650 _ 2 |a Oxidative Stress: physiology
|2 MeSH
650 _ 2 |a Cell Membrane Structures
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700 1 _ |a Eikens, Frederik
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700 1 _ |a Wischhof, Lena
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700 1 _ |a Opitz, Sabine
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700 1 _ |a Jüngling, Kay
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700 1 _ |a Cserép, Csaba
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700 1 _ |a Schmidt, Susanne V
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700 1 _ |a Lambertz, Jessica
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700 1 _ |a Bellande, Tracy
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700 1 _ |a Pósfai, Balázs
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700 1 _ |a Geck, Charlotte
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700 1 _ |a Spitzer, Jasper
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700 1 _ |a Odainic, Alexandru
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700 1 _ |a Castro-Gomez, Mario Sergio
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700 1 _ |a Schwartz, Stephanie
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700 1 _ |a Boussaad, Ibrahim
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700 1 _ |a Krüger, Rejko
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700 1 _ |a Glaab, Enrico
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700 1 _ |a Di Monte, Donato A
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700 1 _ |a Bano, Daniele
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700 1 _ |a Dénes, Ádám
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700 1 _ |a Latz, Eicke
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700 1 _ |a Melki, Ronald
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700 1 _ |a Pape, Hans-Christian
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700 1 _ |a Heneka, Michael T
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773 _ _ |a 10.1016/j.neuron.2024.06.029
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