No ECSIT‐stential evidence for a link with Alzheimer's disease yet (retrospective on DOI 10.1002/bies.201100193)

Illouz, Tomer; Okun, Eitan

doi:10.1002/bies.201400179

Cited by 3 publications

(1 citation statement)

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“…In this study, we demonstrate that dysregulation of the mitochondrial protein ECSIT is associated with the development of AD and contributes to the development of AD-like pathology in animal models. An analysis of reported and predicted ECSIT interactions with redox and mitochondrial proteins encoded by AD susceptibility genes led to the hypothesis that ECSIT might be an interaction hub for many of these proteins, including PSEN1, and could thus play an important role in the etiology of AD 28, 29, 62, 63 . A role for mitochondrial dysfunction and mitochondrial ROS in AD had been suggested based on multiple studies, leading to the “mitochondrial cascade hypothesis” 4–7, 11, 33, 64 .…”

Section: Discussionmentioning

confidence: 99%

ECSIT prevents Alzheimer’s disease pathology by regulating neuronal mitochondrial ROS and mitophagy

Lepelley

Vaughn

Staniszewski

et al. 2020

Preprint

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Altered mitochondrial fitness is a potential triggering factor in Alzheimer’s disease (AD). Mitochondrial quality control pathways are dysfunctional and mitochondrially-derived reactive oxygen species (mROS) levels are increased in AD patient brains. However, the pathways responsible for dysregulated mROS accumulation have remained relatively unclear. In this study, we demonstrate that levels of ECSIT, a mitochondrial oxidative phosphorylation (OxPhos) complex I (CI)-associated protein, are reduced in AD-affected brains. Neuronal ECSIT downregulation increased mROS generation and impaired mitophagy of defective mitochondria. Consequently, decreasing neuronal ECSIT caused AD-like changes, including memory loss and neuropathology. In contrast, augmented neuronal expression of ECSIT protected against the development of an AD-like phenotype. Decreased levels of ECSIT in AD patient brains therefore likely contribute to oxidative stress, neuroinflammation and AD pathogenesis.

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