Mitochondria-targeted catalase reduces abnormal APP processing, amyloid   production and BACE1 in a mouse model of Alzheimer's disease: implications for neuroprotection and lifespan extension

Mao, Peizhong; Mańczak, Maria; Calkins, Marcus J.; Truong, Quang B.; Reddy, T. P.; Reddy, Arubala P.; Shirendeb, Ulziibat; Lo, Herng Hsiang; Rabinovitch, Peter S.; Reddy, P. Hemachandra

doi:10.1093/hmg/dds128

Cited by 161 publications

(117 citation statements)

References 63 publications

(83 reference statements)

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“…mCAT expression resulted in increased longevity without interference on major transduction pathways. Life span extension in mCAT mice was associated with reduced cardiac pathology, decreased DNA oxidative damage, protection against age‐related insulin resistance, and improved proteostasis, underscoring the role of cumulative oxidative damage in aging associated pathologies (Lee et al, 2010; Mao et al, 2012; Treuting et al, 2008; Umanskaya et al, 2014). To further understand the role of Nrf2 stabilization in homeostasis and survival of trisomic cells, we assessed the Nrf2 signaling pathway as well as the effect of mCAT in DS human fibroblasts (HF), and mouse embryonic fibroblasts (MEF) derived from Dp16 mice, a segmentally trisomic model that reproduces several clinical phenotypes present in people with DS, including cognitive impairment (Belichenko et al, 2015; Li et al, 2007; Yu et al, 2010).…”

Section: Introductionmentioning

confidence: 94%

“…An expanding number of studies have reported the presence of chronic oxidative stress and mitochondrial dysfunction in DS at both the cellular and organismal levels (Annerén & Epstein, 1987; Busciglio & Yankner, 1995; Antonarakis et al, 2004; Lott & Dierssen, 2012; Campos et al, 2011). Recently, we reported that decreased mitochondrial activity, increased ROS and mitochondrial fragmentation in DS cells are associated with transcriptional activation of the nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) signaling pathway (Helguera et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Nrf2 stabilization prevents critical oxidative damage in Down syndrome cells

Zamponi

Coşkun

et al. 2018

Aging Cell

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SummaryMounting evidence implicates chronic oxidative stress as a critical driver of the aging process. Down syndrome (DS) is characterized by a complex phenotype, including early senescence. DS cells display increased levels of reactive oxygen species (ROS) and mitochondrial structural and metabolic dysfunction, which are counterbalanced by sustained Nrf2‐mediated transcription of cellular antioxidant response elements (ARE). Here, we show that caspase 3/PKCδdependent activation of the Nrf2 pathway in DS and Dp16 (a mouse model of DS) cells is necessary to protect against chronic oxidative damage and to preserve cellular functionality. Mitochondria‐targeted catalase (mCAT) significantly reduced oxidative stress, restored mitochondrial structure and function, normalized replicative and wound healing capacity, and rendered the Nrf2‐mediated antioxidant response dispensable. These results highlight the critical role of Nrf2/ARE in the maintenance of DS cell homeostasis and validate mitochondrial‐specific interventions as a key aspect of antioxidant and antiaging therapies.

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Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Nrf2 stabilization prevents critical oxidative damage in Down syndrome cells

Zamponi

Coşkun

et al. 2018

Aging Cell

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“…The primary effect of Ab on mitochondria may be to increase ROS production (Manczak et al, 2006), because mitochondrial targeted antioxidants can rescue most aspects of mitochondrial dysfunction Manczak et al, 2010;Mao et al, 2012). Mitochondrial dysfunction may be caused by a direct effect of Ab on electron transport chain function (Crouch et al, 2005).…”

Section: Mitochondrial Function In App Sw -Expressing Mice and Cellsmentioning

confidence: 99%

Caffeine increases mitochondrial function and blocks melatonin signaling to mitochondria in Alzheimer's mice and cells

et al. 2012

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“…Notably, it has been reported that using such monoclonal antibody/kit already sensitively detected that plasma Aβ42 is significantly elevated in late onset AD (Aβ42 levels than controls, p < 0.0001, but Aβ40 p = 0.2) [8,116]. We recently verified that this Aβ42 highly specific antibody also works well in immunohistochemistry [117]. However, it seems that the polyclonal antibodies and related assay kits are more than monoclonal ones in the current market.…”

Section: Problems Concerns and Charlenges In Csf Biomarkersmentioning

confidence: 70%

Recent progress and concerns in dementia: Distinguishing Alzheimer's disease and dementia with Lewy bodies via biochemical markers in the cerebrospinal fluid

Mao¹

2012

ABC

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Dementia is mainly a neurodegenerative disorder involved in several systems, including central nervous system, endocrinology/metabolism system and circulatory system. Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are the most common forms of the dementia, accounting for 60% -80% and 10% -20% of all cases, respectively. DLB is defined by widespread neocortical, limbic and brainstem Lewy bodies but frequently accompanied by variable levels of AD pathology. This pathological and clinical overlap makes their differential diagnosis complicated. Recent advances in the identification of disease biomarkers now make it possible to detect and distinguish their pathology in the early or preclinical stage of the diseases, even in cognitively normal individuals. In addition to the key biomarkers (amyloid β or Aβ, tau and α-synuclein), neurotrophins such as cocaineand amphetamine-regulated transcript (CART) have also drawn attention due to their expressions and functions. This article summarizes the progress in the definition, pathology and diagnosis of dementia, with a focus on potential biochemical markers in the cerebrospinal fluid (CSF) in the differential diagnosis of the main forms of dementia. To prediction or early diagnosis of dementia, the role of specific and sensitive CSF biomarkers seems to be crucial in a routine clinical setting. The concerns and challenges in the biomarker field are also discussed.

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Mitochondria-targeted catalase reduces abnormal APP processing, amyloid production and BACE1 in a mouse model of Alzheimer's disease: implications for neuroprotection and lifespan extension

Cited by 161 publications

References 63 publications

Nrf2 stabilization prevents critical oxidative damage in Down syndrome cells

Nrf2 stabilization prevents critical oxidative damage in Down syndrome cells

Caffeine increases mitochondrial function and blocks melatonin signaling to mitochondria in Alzheimer's mice and cells

Recent progress and concerns in dementia: Distinguishing Alzheimer's disease and dementia with Lewy bodies via biochemical markers in the cerebrospinal fluid

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