TY  - JOUR
AU  - Scheiblich, Hannah
AU  - Eikens, Frederik
AU  - Wischhof, Lena
AU  - Opitz, Sabine
AU  - Jüngling, Kay
AU  - Cserép, Csaba
AU  - Schmidt, Susanne V
AU  - Lambertz, Jessica
AU  - Bellande, Tracy
AU  - Pósfai, Balázs
AU  - Geck, Charlotte
AU  - Spitzer, Jasper
AU  - Odainic, Alexandru
AU  - Castro-Gomez, Mario Sergio
AU  - Schwartz, Stephanie
AU  - Boussaad, Ibrahim
AU  - Krüger, Rejko
AU  - Glaab, Enrico
AU  - Di Monte, Donato A
AU  - Bano, Daniele
AU  - Dénes, Ádám
AU  - Latz, Eicke
AU  - Melki, Ronald
AU  - Pape, Hans-Christian
AU  - Heneka, Michael T
TI  - Microglia rescue neurons from aggregate-induced neuronal dysfunction and death through tunneling nanotubes.
JO  - Neuron
VL  - 112
IS  - 18
SN  - 0896-6273
CY  - New York, NY
PB  - Elsevier
M1  - DZNE-2024-01168
SP  - 3106 - 3125.e8
PY  - 2024
AB  - 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.
KW  - Microglia: metabolism
KW  - Microglia: drug effects
KW  - Animals
KW  - Neurons: metabolism
KW  - Neurons: drug effects
KW  - tau Proteins: metabolism
KW  - tau Proteins: genetics
KW  - alpha-Synuclein: metabolism
KW  - alpha-Synuclein: genetics
KW  - Coculture Techniques
KW  - Mice
KW  - Mitochondria: metabolism
KW  - Mitochondria: drug effects
KW  - Humans
KW  - Leucine-Rich Repeat Serine-Threonine Protein Kinase-2: genetics
KW  - Leucine-Rich Repeat Serine-Threonine Protein Kinase-2: metabolism
KW  - Cell Death: drug effects
KW  - Cell Death: physiology
KW  - Nanotubes
KW  - Cells, Cultured
KW  - Cell Communication: physiology
KW  - Cell Communication: drug effects
KW  - Oxidative Stress: drug effects
KW  - Oxidative Stress: physiology
KW  - Cell Membrane Structures
KW  - Lrrk2 G2019S (Other)
KW  - Trem2 (Other)
KW  - alpha-synuclein (Other)
KW  - intercellular transfer (Other)
KW  - microglia (Other)
KW  - mitochondria (Other)
KW  - neurons (Other)
KW  - oxidative stress (Other)
KW  - tau (Other)
KW  - tunneling nanotubes (Other)
KW  - tau Proteins (NLM Chemicals)
KW  - Tunneling Nanotubes (NLM Chemicals)
KW  - alpha-Synuclein (NLM Chemicals)
KW  - Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39059388
DO  - DOI:10.1016/j.neuron.2024.06.029
UR  - https://pub.dzne.de/record/272487
ER  -