Mortalin is regulated by APOE in hippocampus of AD patients and by human APOE in TR mice

Osorio, Cristina; Sullivan, Patrick M.; Dong, He; Mace, Brian; Ervin, John F.; Strittmatter, Warren J.; Álzate, Óscar

doi:10.1016/j.neurobiolaging.2006.08.011

Cited by 60 publications

(63 citation statements)

References 45 publications

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“…For example, recently, it was found that neuronal protein tau is released from living neurons in exosomes Saman et al, 2012), and this secretion is assumed to help spread tau pathology throughout the Alzheimer΄s disease brain (Clavaguera et al, 2009;Frost et al, 2009). Since mortalin isoform expression is altered in AD brains (Osorio et al, 2007), it could influence the composition of exosomal vesicles and contribute to the exosomal release of pathological tau proteins.…”

Section: Resultsmentioning

confidence: 99%

“…Mortalin was the only protein that was found to be differentially expressed in ApoE4 transgenic mice hippocampus compared to ApoE3 mice. Moreover, different phospho-isoforms of mortalin have been found as well (Osorio et al, 2007). In another study a significant upregulation of mortalin gene expression was observed in PC12 cells overexpressing amyloid precursor protein (Kogel et al, 2005).…”

Section: Mortalin and Neurodegenerative Diseasesmentioning

confidence: 90%

“…Mortalin was identified as one of the six oxidation-sensitive proteins by using two-dimensional electrophoresis coupled with immunostaining for protein carbonylation (Choi et al, 2004). Differential protein expression analysis of human AD brain samples revealed differentially expressed mortalin isoforms (Osorio et al, 2007). One of the mortalin isoforms was increased within AD hippocampi compared to the normal tissue.…”

Section: Mortalin and Neurodegenerative Diseasesmentioning

confidence: 99%

“…These alleles are known to be either associated with significantly increased risk of Alzheimer΄s disease in human population (ApoE4) or to have a rather protective role (ApoE3) (Keene et al, 2011). The authors generated a transgenic mouse models by replacing the endogenous mouse ApoE with either human ApoE4 or ApoE3 allele (Osorio et al, 2007). Mortalin was the only protein that was found to be differentially expressed in ApoE4 transgenic mice hippocampus compared to ApoE3 mice.…”

Section: Mortalin and Neurodegenerative Diseasesmentioning

confidence: 99%

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Mortalin – a multipotent chaperone regulating cellular processes ranging from viral infection to neurodegeneration

Flachbartova¹,

Kováčech²

2013

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Summary. -Heat shock 70kDa protein 9 (HSPA9)/mortalin is a heat-uninducible member of the heat shock 70 protein family. This protein has been attributed many cellular functions, including energy generation, stress response, carcinogenesis and involvement in neurodegenerative diseases, which is well documented by many names it has been given (CSA, MOT, MOT2, GRP75, PBP74, GRP-75, HSPA9B, MGC4500, MTHSP75, and mortalin). As an immortalization marker (hence the name "mortalin") in mouse embryonic fibroblasts cybrids it preferentially segregated with loss of immortality in passaged cells. Mortalin regulates the functions of the tumor suppressor protein p53 and plays important roles in stress response and maintenance of the mitochondria and endoplasmic reticulum. Furthermore, mortalin appears to have roles in membrane trafficking and viral release regulation, since it interacts with Nef protein it is necessary for secretion of exosomal negative factor (Nef) and HIV-1 virus release. Recently, mortalin has been described as a significant player in neurodegenerative diseases. Mutations in HSPA9 gene have been found in Parkinson΄s disease patients; mortalin isoform expression differs in hippocampus of patients with Alzheimer΄s disease and could regulate the β-amyloid toxicity pathway. In this review we summarize the functions of mortalin, its pathological implications in neuronal dysfunction and possible roles in neurodegenerative diseases.Keywords: HSPA9/mortalin/GRP75; mitochondria; cancer; Alzheimer΄s disease * Corresponding author: E-mail: Branislav.Kovacech@savba.sk; phone: +412-2-54788100. Abbreviations: Aβ = beta-amyloid; AD = Alzheimer΄s disease; PD = Parkinson΄s disease; HSPA9 = heat shock 70 kDa protein 9; Hsp = chaperone; MAC = membrane attack complex; Net = negative factor Contents:

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Section: Resultsmentioning

confidence: 99%

Section: Mortalin and Neurodegenerative Diseasesmentioning

confidence: 90%

Section: Mortalin and Neurodegenerative Diseasesmentioning

confidence: 99%

Section: Mortalin and Neurodegenerative Diseasesmentioning

confidence: 99%

See 2 more Smart Citations

Mortalin – a multipotent chaperone regulating cellular processes ranging from viral infection to neurodegeneration

Flachbartova¹,

Kováčech²

2013

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“…APP and Aβ have both been localized to mitochondria, where they may cause a disruption of basic mitochondrial functions including oxidative phosphorylation or protein import [82]; similar to HAART. Complex IV (of the electron transport chain) seem to be a direct target of both Aβ and truncated ApoE4 [80,84] well as NRTI.…”

Section: Elevation Of Ros App Processing and Aβ Biogenesismentioning

confidence: 99%

Development of 2′-Deoxy-4′-C-Ethynyl-2-Fluoroadenosine (EFdA) which has Supremely High Anti-HIV Activity and Low Toxicity and Prevents the Emergence of Resistant HIV Mutants, and Discovery of Different Substrate Selectivity between Viral and Human Nucleic Acid Polymerases

Ohrui¹

2013

J Antivir Antiretrovir

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Highly Active Antiretroviral Therapy (HAART) has significantly reduced AIDS-related morbidity and mortality. However the prevalence of HIV-1-Associated Neurocognitive Disorders (HAND) has been on the rise in the post-HAART era. A majority of the side effects of HAART can in part at least be attributed directly, or indirectly, to mitochondrial dysfunction. Indeed the rapid early clinical phase-in of HAART required dose de-escalations secondary to toxicities suggested to be related to drug side effects affecting mitochondria. Central to central nervous system (CNS) function is the amyloid precursor protein (APP), the parent protein from which amyloid-beta (Aβ) peptide is generated. Aβ generation and aggregation as plaques are well known in the age related dementia, Alzheimer's disease (AD). It has been demonstrated that Aβ is common feature of the HIV infected brain as well. Further, reactive oxygen species (ROS) production is upregulated by HAART. Importantly, ROS promote β-secretase expression; a mechanism by which HAART may promote cognitive dysfunction, even in immune-competent HIV infected individuals.

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Alzheimer's disease: are blood and brain markers related? A systematic review

Khan

Dobson

Sattlecker

et al. 2016

Ann Clin Transl Neurol

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a These authors contributed equally to the work. AbstractObjective: Peripheral protein biomarkers of Alzheimer's disease (AD) may help identify novel treatment avenues by allowing early diagnosis, recruitment to clinical trials, and treatment initiation. The purpose of this review was to determine which proteins have been found to be differentially expressed in the AD brain and whether these proteins are also found within the blood of AD patients. Methods: A two-stage approach was conducted. The first stage involved conducting a systematic search to identify discovery-based brain proteomic studies of AD. The second stage involved comparing whether proteins found to be differentially expressed in AD brain were also differentially expressed in the blood. Results: Across 11 discovery based brain proteomic studies 371 proteins were at different levels in the AD brain. Nine proteins were frequently found, defined as appearing in at least three separate studies. Of these proteins heat-shock cognate 71 kDa, ubiquitin carboxyl-terminal hydrolase isozyme L1, and 2 0 ,3 0 -cyclic nucleotide 3 0 phosphodiesterase alone were found to share a consistent direction of change, being consistently upregulated in studies they appeared in. Eighteen proteins seen as being differentially expressed within the AD brain were present in blood proteomic studies of AD. Only complement C4a was seen multiple times within both the blood and brain proteomic studies. Interpretation: We report a number of proteins appearing in both the blood and brain of AD patients. Of these proteins, C4a may be a good candidate for further follow-up in large-scale replication efforts.

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Mortalin is regulated by APOE in hippocampus of AD patients and by human APOE in TR mice

Cited by 60 publications

References 45 publications

Mortalin – a multipotent chaperone regulating cellular processes ranging from viral infection to neurodegeneration

Mortalin – a multipotent chaperone regulating cellular processes ranging from viral infection to neurodegeneration

Development of 2′-Deoxy-4′-C-Ethynyl-2-Fluoroadenosine (EFdA) which has Supremely High Anti-HIV Activity and Low Toxicity and Prevents the Emergence of Resistant HIV Mutants, and Discovery of Different Substrate Selectivity between Viral and Human Nucleic Acid Polymerases

Alzheimer's disease: are blood and brain markers related? A systematic review

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