Journal Article

DZNE-2024-01168

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Microglia rescue neurons from aggregate-induced neuronal dysfunction and death through tunneling nanotubes.

Scheiblich, H. (First author)DZNE* ; Eikens, F.DZNE* ; Wischhof, L.DZNE* ; Opitz, S. ; Jüngling, K. ; Cserép, C. ; Schmidt, S. V. ; Lambertz, J. ; Bellande, T. ; Pósfai, B. ; Geck, C. ; Spitzer, J. ; Odainic, A. ; Castro-Gomez, M. S.Extern* ; Schwartz, S. ; Boussaad, I. ; Krüger, R. ; Glaab, E. ; Di Monte, D. A.DZNE* ; Bano, D.DZNE* ; Dénes, Á. ; Latz, E.DZNE* ; Melki, R. ; Pape, H.-C. ; Heneka, M. T. (Last author)DZNE*

2024
Elsevier New York, NY

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Please use a persistent id in citations: doi:10.1016/j.neuron.2024.06.029

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.

Keyword(s): Microglia: metabolism (MeSH) ; Microglia: drug effects (MeSH) ; Animals (MeSH) ; Neurons: metabolism (MeSH) ; Neurons: drug effects (MeSH) ; tau Proteins: metabolism (MeSH) ; tau Proteins: genetics (MeSH) ; alpha-Synuclein: metabolism (MeSH) ; alpha-Synuclein: genetics (MeSH) ; Coculture Techniques (MeSH) ; Mice (MeSH) ; Mitochondria: metabolism (MeSH) ; Mitochondria: drug effects (MeSH) ; Humans (MeSH) ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2: genetics (MeSH) ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2: metabolism (MeSH) ; Cell Death: drug effects (MeSH) ; Cell Death: physiology (MeSH) ; Nanotubes (MeSH) ; Cells, Cultured (MeSH) ; Cell Communication: physiology (MeSH) ; Cell Communication: drug effects (MeSH) ; Oxidative Stress: drug effects (MeSH) ; Oxidative Stress: physiology (MeSH) ; Cell Membrane Structures (MeSH) ; Lrrk2 G2019S ; Trem2 ; alpha-synuclein ; intercellular transfer ; microglia ; mitochondria ; neurons ; oxidative stress ; tau ; tunneling nanotubes ; tau Proteins ; Tunneling Nanotubes ; alpha-Synuclein ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2

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Contributing Institute(s):

1. Neuroinflammation, Biomarker (AG Heneka)
2. Aging and Neurodegeneration (AG Bano)
3. Neurodegeneration and Neuroprotection in Parkinson´s Disease (AG Di Monte)
4. Innate Immunity in Neurodegeneration (AG Latz)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
2. 351 - Brain Function (POF4-351) (POF4-351)
3. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2024

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 15 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Journal Article Neher, J. J. (First author)DZNE* ; Simons, M. (Last author)DZNE*
Protective lifelines: Tunneling nanotubes connect neurons and microglia.
Neuron 112(18), 2991 - 2993 (2024) [10.1016/j.neuron.2024.07.027]2024   Files BibTeX | EndNote: XML, Text | RIS

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