Idioma:

Mitochondrial hypermetabolism precedes impaired autophagy and synaptic disorganization in App knock-in Alzheimer mouse models

Naia, Luana ; Shimozawa, Makoto ; Bereczki, Erika ; Li, Xidan ; Liu, Jianping ; Jiang, Richeng ; Giraud, Romain ; Leal, Nuno Santos ; Pinho, Catarina Moreira ; Berger, Erik ; Falk, Victoria Lim ; Dentoni, Giacomo ; Ankarcrona, Maria ; Nilsson, Per

Molecular psychiatry, 2023-09, Vol.28 (9), p.3966-3981 [Periódico revisado por pares]

England: Nature Publishing Group

Texto completo disponível

Citações Citado por

Enviar para

Título:
Mitochondrial hypermetabolism precedes impaired autophagy and synaptic disorganization in App knock-in Alzheimer mouse models
Autor: Naia, Luana ; Shimozawa, Makoto ; Bereczki, Erika ; Li, Xidan ; Liu, Jianping ; Jiang, Richeng ; Giraud, Romain ; Leal, Nuno Santos ; Pinho, Catarina Moreira ; Berger, Erik ; Falk, Victoria Lim ; Dentoni, Giacomo ; Ankarcrona, Maria ; Nilsson, Per
Assuntos: Alzheimer Disease - metabolism ; Alzheimer's disease ; Amyloid beta-Peptides - metabolism ; Amyloid beta-Protein Precursor - genetics ; Amyloid precursor protein ; Animal models ; Animals ; Autophagy ; Autophagy - genetics ; Disease Models, Animal ; Energy metabolism ; Hippocampus ; Medicin och hälsovetenskap ; Metabolism ; Mice ; Mice, Transgenic ; Mitochondria ; Mobile Applications ; Neurodegenerative diseases ; Oxidative phosphorylation ; Pathology ; Phagosomes ; Phosphorylation ; Synaptic vesicles ; Transcriptomes ; β-Amyloid
É parte de: Molecular psychiatry, 2023-09, Vol.28 (9), p.3966-3981
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Descrição: Accumulation of amyloid β-peptide (Aβ) is a driver of Alzheimer's disease (AD). Amyloid precursor protein (App) knock-in mouse models recapitulate AD-associated Aβ pathology, allowing elucidation of downstream effects of Aβ accumulation and their temporal appearance upon disease progression. Here we have investigated the sequential onset of AD-like pathologies in App and App knock-in mice by time-course transcriptome analysis of hippocampus, a region severely affected in AD. Strikingly, energy metabolism emerged as one of the most significantly altered pathways already at an early stage of pathology. Functional experiments in isolated mitochondria from hippocampus of both App and App mice confirmed an upregulation of oxidative phosphorylation driven by the activity of mitochondrial complexes I, IV and V, associated with higher susceptibility to oxidative damage and Ca -overload. Upon increasing pathologies, the brain shifts to a state of hypometabolism with reduced abundancy of mitochondria in presynaptic terminals. These late-stage mice also displayed enlarged presynaptic areas associated with abnormal accumulation of synaptic vesicles and autophagosomes, the latter ultimately leading to local autophagy impairment in the synapses. In summary, we report that Aβ-induced pathways in App knock-in mouse models recapitulate key pathologies observed in AD brain, and our data herein adds a comprehensive understanding of the pathologies including dysregulated metabolism and synapses and their timewise appearance to find new therapeutic approaches for AD.
Editor: England: Nature Publishing Group
Idioma: Inglês

Links

Voltar para lista de resultados

Realização: Logos de Redes Sociais:

Mitochondrial hypermetabolism precedes impaired autophagy and synaptic disorganization in App knock-in Alzheimer mouse models

Naia, Luana ; Shimozawa, Makoto ; Bereczki, Erika ; Li, Xidan ; Liu, Jianping ; Jiang, Richeng ; Giraud, Romain ; Leal, Nuno Santos ; Pinho, Catarina Moreira ; Berger, Erik ; Falk, Victoria Lim ; Dentoni, Giacomo ; Ankarcrona, Maria ; Nilsson, Per

England: Nature Publishing Group

Buscando em bases de dados remotas. Favor aguardar.