ArticleJournal of Alzheimer's disease : JAD2011
Decreased proteolytic activity of the mitochondrial amyloid-β degrading enzyme, PreP peptidasome, in Alzheimer's disease brain mitochondria.
Article in Journal of Alzheimer's disease : JAD, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
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Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.
- Multivariate meta-analyses of mitochondrial complex I and IV in major depressive disorder, bipolar disorder, schizophrenia, Alzheimer disease, and Parkinson disease.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Pooled it
- The mitochondrial unfolded protein response in human microglia disrupts neuronal-glial communication and promotes senescence.Nature neuroscience · 2026Article
- Mitochondrial proteases and their roles in mitophagy in plants, animals, and yeast.Plant & cell physiology · 2025Review
- Therapeutic potential of melatonin-induced mitophagy in the pathogenesis of Alzheimer's disease.Inflammopharmacology · 2025Review
- Review
- The Azalea Hypothesis of Alzheimer Disease: A Functional Iron Deficiency Promotes Neurodegeneration.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2024Review
- Mitochondria in Alzheimer's Disease Pathogenesis.Life (Basel, Switzerland) · 2024Review
- Recent Advances in the Treatment and Management of Alzheimer's Disease: A Precision Medicine Perspective.Current topics in medicinal chemistry · 2024Review
- Mitophagy in Alzheimer's Disease: A Bibliometric Analysis from 2007 to 2022.Journal of Alzheimer's disease reports · 2024Article
- Mitochondrial Complex I and β-Amyloid Peptide Interplay in Alzheimer's Disease: A Critical Review of New and Old Little Regarded Findings.International journal of molecular sciences · 2023Review
- Advances in Amyloid-β Clearance in the Brain and Periphery: Implications for Neurodegenerative Diseases.Experimental neurobiology · 2023Review
- Review
- Targeting Mitochondrial Oxidative Stress as a Strategy to Treat Aging and Age-Related Diseases.Antioxidants (Basel, Switzerland) · 2023Review
- Exploring Whether Iron Sequestration within the CNS of Patients with Alzheimer's Disease Causes a Functional Iron Deficiency That Advances Neurodegeneration.Brain sciences · 2023Article
- Disturb mitochondrial associated proteostasis: Neurodegeneration and imperfect ageing.Frontiers in cell and developmental biology · 2023Review
- Interactions of amyloidogenic proteins with mitochondrial protein import machinery in aging-related neurodegenerative diseases.Frontiers in physiology · 2023Review
- Structural basis for the mechanisms of human presequence protease conformational switch and substrate recognition.Nature communications · 2022Article
- In vivo alterations of mitochondrial activity and amyloidosis in early-stage senescence-accelerated mice: a positron emission tomography study.Journal of neuroinflammation · 2021Article
- In-frame deletion in canine PITRM1 is associated with a severe early-onset epilepsy, mitochondrial dysfunction and neurodegeneration.Human genetics · 2021Article
- Role of PITRM1 in Mitochondrial Dysfunction and Neurodegeneration.Biomedicines · 2021Review
4 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Accumulation of amyloid-β peptide (Aβ), the neurotoxic peptide implicated in the pathogenesis of Alzheimer's disease (AD), has been shown in brain mitochondria of AD patients and of AD transgenic mouse models. The presence of Aβ in mitochondria leads to free radical generation and neuronal stress. Recently, we identified the presequence protease, PreP, localized in the mitochondrial matrix in mammalian mitochondria as the novel mitochondrial Aβ-degrading enzyme. In the present study, we examined PreP activity in the mitochondrial matrix of the human brain's temporal lobe, an area of the brain highly susceptible to Aβ accumulation and reactive oxygen species (ROS) production. We found significantly lower hPreP activity in AD brains compared with non-AD age-matched controls. By contrast, in the cerebellum, a brain region typically spared from Aβ accumulation, there was no significant difference in hPreP activity when comparing AD samples to non-AD controls. We also found significantly reduced PreP activity in the mitochondrial matrix of AD transgenic mouse brains (Tg mAβPP and Tg mAβPP/ABAD) when compared to non-transgenic aged-matched mice. Furthermore, mitochondrial fractions isolated from AD brains and Tg mAβPP mice had higher levels of 4-hydroxynonenal, an oxidative product, as compared with those from non-AD and nonTg mice. Accordingly, activity of cytochrome c oxidase was significantly reduced in the AD mitochondria. These findings suggest that decreased PreP proteolytic activity, possibly due to enhanced ROS production, contributes to Aβ accumulation in mitochondria leading to the mitochondrial toxicity and neuronal death that is exacerbated in AD. Clearance of mitochondrial Aβ by PreP may thus be of importance in the pathology of AD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.