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@ARTICLE{Scheiblich:272487,
author = {Scheiblich, Hannah and Eikens, Frederik and Wischhof, Lena
and Opitz, Sabine and Jüngling, Kay and Cserép, Csaba and
Schmidt, Susanne V and Lambertz, Jessica and Bellande, Tracy
and Pósfai, Balázs and Geck, Charlotte and Spitzer, Jasper
and Odainic, Alexandru and Castro-Gomez, Mario Sergio and
Schwartz, Stephanie and Boussaad, Ibrahim and Krüger, Rejko
and Glaab, Enrico and Di Monte, Donato A and Bano, Daniele
and Dénes, Ádám and Latz, Eicke and Melki, Ronald and
Pape, Hans-Christian and Heneka, Michael T},
title = {{M}icroglia rescue neurons from aggregate-induced neuronal
dysfunction and death through tunneling nanotubes.},
journal = {Neuron},
volume = {112},
number = {18},
issn = {0896-6273},
address = {New York, NY},
publisher = {Elsevier},
reportid = {DZNE-2024-01168},
pages = {3106 - 3125.e8},
year = {2024},
abstract = {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.},
keywords = {Microglia: metabolism / Microglia: drug effects / Animals /
Neurons: metabolism / Neurons: drug effects / tau Proteins:
metabolism / tau Proteins: genetics / alpha-Synuclein:
metabolism / alpha-Synuclein: genetics / Coculture
Techniques / Mice / Mitochondria: metabolism / Mitochondria:
drug effects / Humans / Leucine-Rich Repeat Serine-Threonine
Protein Kinase-2: genetics / Leucine-Rich Repeat
Serine-Threonine Protein Kinase-2: metabolism / Cell Death:
drug effects / Cell Death: physiology / Nanotubes / Cells,
Cultured / Cell Communication: physiology / Cell
Communication: drug effects / Oxidative Stress: drug effects
/ Oxidative Stress: physiology / Cell Membrane Structures /
Lrrk2 G2019S (Other) / Trem2 (Other) / alpha-synuclein
(Other) / intercellular transfer (Other) / microglia (Other)
/ mitochondria (Other) / neurons (Other) / oxidative stress
(Other) / tau (Other) / tunneling nanotubes (Other) / tau
Proteins (NLM Chemicals) / Tunneling Nanotubes (NLM
Chemicals) / alpha-Synuclein (NLM Chemicals) / Leucine-Rich
Repeat Serine-Threonine Protein Kinase-2 (NLM Chemicals)},
cin = {AG Heneka / AG Bano / AG Di Monte / AG Latz},
ddc = {610},
cid = {I:(DE-2719)1011303 / I:(DE-2719)1013003 /
I:(DE-2719)1013008 / I:(DE-2719)1013024},
pnm = {353 - Clinical and Health Care Research (POF4-353) / 351 -
Brain Function (POF4-351) / 352 - Disease Mechanisms
(POF4-352)},
pid = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-351 /
G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39059388},
doi = {10.1016/j.neuron.2024.06.029},
url = {https://pub.dzne.de/record/272487},
}