Mitophagy alterations in Alzheimer's disease are associated with granulovacuolar degeneration and early tau pathology

The cytoprotective PTEN‐induced kinase 1 (PINK1)‐parkin RBR E3 ubiquitin protein ligase (PRKN) pathway selectively labels damaged mitochondria with phosphorylated ubiquitin (pS65‐Ub) for their autophagic removal (mitophagy). Because dysfunctions of mitochondria and degradation pathways are early features of Alzheimer's disease (AD), mitophagy impairments may contribute to the pathogenesis.

[1]  D. Dickson,et al.  Sensitive ELISA-based detection method for the mitophagy marker p-S65-Ub in human cells, autopsy brain, and blood samples , 2020, Autophagy.

[2]  W. Scheper,et al.  Granulovacuolar degeneration bodies are neuron-selective lysosomal structures induced by intracellular tau pathology , 2019, Acta Neuropathologica.

[3]  Sean C. Bendall,et al.  The basis of cellular and regional vulnerability in Alzheimer’s disease , 2019, Acta Neuropathologica.

[4]  N. Sawamoto,et al.  Phosphorylated NF-κB subunit p65 aggregates in granulovacuolar degeneration and neurites in neurodegenerative diseases with tauopathy , 2019, Neuroscience Letters.

[5]  T. Sargeant,et al.  Rapamycin and Alzheimer disease: a double-edged sword? , 2019, Autophagy.

[6]  M. Z. Cader,et al.  Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer’s disease , 2019, Nature Neuroscience.

[7]  J. Bertran-Gonzalez,et al.  Disease‐associated tau impairs mitophagy by inhibiting Parkin translocation to mitochondria , 2018, The EMBO journal.

[8]  R. Nixon,et al.  Transgenic expression of a ratiometric autophagy probe specifically in neurons enables the interrogation of brain autophagy in vivo , 2018, Autophagy.

[9]  John Hardy,et al.  Selective vulnerability in neurodegenerative diseases , 2018, Nature Neuroscience.

[10]  M. Farrer,et al.  Age- and disease-dependent increase of the mitophagy marker phospho-ubiquitin in normal aging and Lewy body disease , 2018, Autophagy.

[11]  G. Bu,et al.  ApoE4 Accelerates Early Seeding of Amyloid Pathology , 2017, Neuron.

[12]  L. Lue,et al.  PINK1 signalling rescues amyloid pathology and mitochondrial dysfunction in Alzheimer’s disease , 2017, Brain : a journal of neurology.

[13]  R. Nixon.  Amyloid precursor protein and endosomal‐lysosomal dysfunction in Alzheimer's disease: inseparable partners in a multifactorial disease , 2017, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[14]  M. Z. Cader,et al.  Mitophagy and Alzheimer’s Disease: Cellular and Molecular Mechanisms , 2017, Trends in Neurosciences.

[15]  T. Caulfield,et al.  PINK1, Parkin, and Mitochondrial Quality Control: What can we Learn about Parkinson’s Disease Pathobiology? , 2016, Journal of Parkinson's disease.

[16]  S. Ginsberg,et al.  Autophagy flux in CA1 neurons of Alzheimer hippocampus: Increased induction overburdens failing lysosomes to propel neuritic dystrophy , 2016, Autophagy.

[17]  L. Ang,et al.  Granulovacuolar Degeneration in Hippocampus of Neurodegenerative Diseases: Quantitative Study , 2016, Journal of neurodegenerative diseases.

[18]  Michael J. Munson,et al.  mito-QC illuminates mitophagy and mitochondrial architecture in vivo , 2016, The Journal of cell biology.

[19]  C. Köhler.  Granulovacuolar degeneration: a neurodegenerative change that accompanies tau pathology , 2016, Acta Neuropathologica.

[20]  J. Ávila,et al.  PARK2 enhancement is able to compensate mitophagy alterations found in sporadic Alzheimer's disease. , 2016, Human molecular genetics.

[21]  Y. Yoo,et al.  Measuring In Vivo Mitophagy. , 2015, Molecular cell.

[22]  F. Fiesel,et al.  Disease relevance of phosphorylated ubiquitin (p-S65-Ub) , 2015, Autophagy.

[23]  Elisabeth L. Moussaud-Lamodière,et al.  (Patho‐)physiological relevance of PINK1‐dependent ubiquitin phosphorylation , 2015, EMBO reports.

[24]  S. Lincoln,et al.  Progressive dopaminergic alterations and mitochondrial abnormalities in LRRK2 G2019S knock-in mice , 2015, Neurobiology of Disease.

[25]  Clifford R. Jack,et al.  Clinicopathologic and 11C-Pittsburgh compound B implications of Thal amyloid phase across the Alzheimer’s disease spectrum , 2015, Brain : a journal of neurology.

[26]  A. Borreca,et al.  NH2-truncated human tau induces deregulated mitophagy in neurons by aberrant recruitment of Parkin and UCHL-1: implications in Alzheimer's disease. , 2015, Human molecular genetics.

[27]  Qian Cai,et al.  Parkin-mediated mitophagy in mutant hAPP neurons and Alzheimer's disease patient brains. , 2015, Human molecular genetics.

[28]  R. Swerdlow,et al.  The Alzheimer's disease mitochondrial cascade hypothesis: progress and perspectives. , 2014, Biochimica et biophysica acta.

[29]  Mei Yu,et al.  Parkin overexpression ameliorates hippocampal long-term potentiation and β-amyloid load in an Alzheimer's disease mouse model. , 2014, Human molecular genetics.

[30]  T. Saido,et al.  Aβ secretion and plaque formation depend on autophagy. , 2013, Cell reports.

[31]  E. Klann,et al.  Macroautophagy deficiency mediates age-dependent neurodegeneration through a phospho-tau pathway , 2012, Molecular Neurodegeneration.

[32]  T. Yamawaki,et al.  Granulovacuolar Degenerations Appear in Relation to Hippocampal Phosphorylated Tau Accumulation in Various Neurodegenerative Disorders , 2011, PloS one.

[33]  Hyoung-Gon Lee,et al.  A Novel Origin for Granulovacuolar Degeneration in Aging and Alzheimer’s Disease: Parallels to Stress Granules , 2011, Laboratory Investigation.

[34]  H. Braak,et al.  Stages of granulovacuolar degeneration: their relation to Alzheimer’s disease and chronic stress response , 2011, Acta Neuropathologica.

[35]  Sooyeon Lee,et al.  Lysosomal Proteolysis Inhibition Selectively Disrupts Axonal Transport of Degradative Organelles and Causes an Alzheimer's-Like Axonal Dystrophy , 2011, The Journal of Neuroscience.

[36]  J. Kuret,et al.  Granulovacuolar degeneration (GVD) bodies of Alzheimer's disease (AD) resemble late‐stage autophagic organelles , 2011, Neuropathology and applied neurobiology.

[37]  G. Gibson,et al.  A mitocentric view of Alzheimer's disease suggests multi-faceted treatments. , 2010, Journal of Alzheimer's disease : JAD.

[38]  E. Mandelkow,et al.  Tau fragmentation, aggregation and clearance: the dual role of lysosomal processing. , 2009, Human molecular genetics.

[39]  M. Jendrach,et al.  Mitochondrial dysfunction: An early event in Alzheimer pathology accumulates with age in AD transgenic mice , 2009, Neurobiology of Aging.

[40]  M. Lovell,et al.  Quantitative Proteomic Analysis of Mitochondria in Aging PS-1 Transgenic Mice , 2009, Cellular and Molecular Neurobiology.

[41]  R. Guerrero,et al.  Hyperphosphorylated tau aggregates in the cortex and hippocampus of transgenic mice with mutant human FTDP-17 Tau and lacking the PARK2 gene , 2009, Acta Neuropathologica.

[42]  M. Mena,et al.  Parkin deletion causes cerebral and systemic amyloidosis in human mutated tau over-expressing mice. , 2008, Human molecular genetics.

[43]  Ralph A. Nixon,et al.  Autophagy Induction and Autophagosome Clearance in Neurons: Relationship to Autophagic Pathology in Alzheimer's Disease , 2008, The Journal of Neuroscience.

[44]  M. Beal,et al.  Amyloid beta, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer's disease. , 2008, Trends in molecular medicine.

[45]  K. Ashe,et al.  Age-Dependent Neurofibrillary Tangle Formation, Neuron Loss, and Memory Impairment in a Mouse Model of Human Tauopathy (P301L) , 2005, The Journal of Neuroscience.

[46]  Ralph A. Nixon,et al.  Extensive Involvement of Autophagy in Alzheimer Disease: An Immuno-Electron Microscopy Study , 2005, Journal of neuropathology and experimental neurology.

[47]  T. Inagaki,et al.  Granulovacuolar degeneration in the hippocampal cortex of aging and demented patients — a quantitative study , 1992, Acta Neuropathologica.

[48]  S. Hirai,et al.  Reexamination of granulovacuolar degeneration , 2004, Acta Neuropathologica.

[49]  J. Kuret,et al.  A new molecular link between the fibrillar and granulovacuolar lesions of Alzheimer's disease. , 1999, The American journal of pathology.

[50]  Allan I. Levey,et al.  Familial Alzheimer's Disease–Linked Presenilin 1 Variants Elevate Aβ1–42/1–40 Ratio In Vitro and In Vivo , 1996, Neuron.

[51]  Peter Davies,et al.  Identification of normal and pathological aging in prospectively studied nondemented elderly humans , 1992, Neurobiology of Aging.