Phosphorylated tau interactome in the human Alzheimer’s disease brain DOI Open Access
Eleanor Drummond, Geoffrey Pires, Claire MacMurray

и другие.

Brain, Год журнала: 2020, Номер 143(9), С. 2803 - 2817

Опубликована: Июнь 23, 2020

Accumulation of phosphorylated tau is a key pathological feature Alzheimer's disease. Phosphorylated accumulation causes synaptic impairment, neuronal dysfunction and formation neurofibrillary tangles. The actions are mediated by surrounding proteins; however, comprehensive understanding the proteins that interacts with in disease surprisingly limited. Therefore, aim this study was to determine interactome. To end, we used two complementary proteomics approaches: (i) quantitative performed on tangles microdissected from patients advanced disease; (ii) affinity purification-mass spectrometry identify which these specifically bound tau. We identified 542 This included abundant detection many known be present such as tau, ubiquitin, neurofilament apolipoprotein E. Affinity confirmed 75 interacted PHF1-immunoreactive Twenty-nine have been previously associated therefore validating our proteomic approach. More importantly, 34 had total but not yet linked directly (e.g. protein VAMP2, vacuolar-ATPase subunit ATP6V0D1); therefore, provide new evidence they interact In addition, also 12 novel proteins, physiologically or pathologically RNA binding HNRNPA1). Network analysis showed interactome enriched involved ubiquitination pathway phagosome maturation. Importantly, were able pinpoint specific pathways for first time, providing potential pathogenic mechanisms can explored future studies. Combined, results reveal drug targets treatment tauopathies insight into how mediates its toxicity

Язык: Английский

The CAMKK2-AMPK Kinase Pathway Mediates the Synaptotoxic Effects of Aβ Oligomers through Tau Phosphorylation DOI Creative Commons

Georges Mairet‐Coello,

Julien Courchet, Simon Pieraut

и другие.

Neuron, Год журнала: 2013, Номер 78(1), С. 94 - 108

Опубликована: Апрель 1, 2013

Язык: Английский

Процитировано

319

Soluble amyloid-β oligomers as synaptotoxins leading to cognitive impairment in Alzheimer’s disease DOI Creative Commons
Sérgio T. Ferreira, Mychael V. Lourenco, Maurício M. Oliveira

и другие.

Frontiers in Cellular Neuroscience, Год журнала: 2015, Номер 9

Опубликована: Май 26, 2015

Alzheimer’s disease (AD) is the most common form of dementia in elderly, and affects millions people worldwide. As number AD cases continues to increase both developed developing countries, finding therapies that effectively halt or reverse progression constitutes a major research public health challenge. Since identification amyloid-b peptide (Ab) as component amyloid plaques are characteristically found brains, effort has aimed determine whether how Ab leads memory loss cognitive impairment. A large body evidence accumulated past 15 years supports pivotal role soluble oligomers (AbOs) synapse failure neuronal dysfunction AD. Nonetheless, basic questions, including exact molecular composition synaptotoxic oligomers, identity receptor(s) which they bind, signaling pathways ultimately lead failure, remain be definitively answered. Here, we discuss recent advances have illuminated our understanding chemical nature toxic species deleterious impact on synapses, culminated proposal an oligomer hypothesis for pathogenesis. We also highlight outstanding questions challenges should addressed allow translation findings into effective therapies.

Язык: Английский

Процитировано

313

Hsp90-Tau Complex Reveals Molecular Basis for Specificity in Chaperone Action DOI Creative Commons
G Elif Karagöz, Afonso M.S. Duarte, Elias Akoury

и другие.

Cell, Год журнала: 2014, Номер 156(5), С. 963 - 974

Опубликована: Фев. 1, 2014

Язык: Английский

Процитировано

305

Wnt signaling in the nervous system and in Alzheimer's disease DOI Open Access

Nibaldo C. Inestrosa,

Lorena Varela‐Nallar

Journal of Molecular Cell Biology, Год журнала: 2014, Номер 6(1), С. 64 - 74

Опубликована: Фев. 1, 2014

Wnts comprise a large family of proteins that have shown to be part signaling cascade regulates several aspects development including organogenesis, midbrain as well stem cell proliferation. Wnt pathway plays different roles in the neuronal circuits and also adult brain, where it synaptic transmission plasticity. It has been implicated various diseases cancer neurodegenerative diseases, reflecting its relevance fundamental biological processes. This review summarizes progress about function mature nervous system with focus on Alzheimer's disease (AD). We discuss prospects modulating canonical non-canonical strategy for neuroprotection. will include potential to: (i) act potent regulators hippocampal synapses impact learning memory; (ii) regulate neurogenesis; finally (iii) control AD pathogenesis.

Язык: Английский

Процитировано

289

Phosphorylated tau interactome in the human Alzheimer’s disease brain DOI Open Access
Eleanor Drummond, Geoffrey Pires, Claire MacMurray

и другие.

Brain, Год журнала: 2020, Номер 143(9), С. 2803 - 2817

Опубликована: Июнь 23, 2020

Accumulation of phosphorylated tau is a key pathological feature Alzheimer's disease. Phosphorylated accumulation causes synaptic impairment, neuronal dysfunction and formation neurofibrillary tangles. The actions are mediated by surrounding proteins; however, comprehensive understanding the proteins that interacts with in disease surprisingly limited. Therefore, aim this study was to determine interactome. To end, we used two complementary proteomics approaches: (i) quantitative performed on tangles microdissected from patients advanced disease; (ii) affinity purification-mass spectrometry identify which these specifically bound tau. We identified 542 This included abundant detection many known be present such as tau, ubiquitin, neurofilament apolipoprotein E. Affinity confirmed 75 interacted PHF1-immunoreactive Twenty-nine have been previously associated therefore validating our proteomic approach. More importantly, 34 had total but not yet linked directly (e.g. protein VAMP2, vacuolar-ATPase subunit ATP6V0D1); therefore, provide new evidence they interact In addition, also 12 novel proteins, physiologically or pathologically RNA binding HNRNPA1). Network analysis showed interactome enriched involved ubiquitination pathway phagosome maturation. Importantly, were able pinpoint specific pathways for first time, providing potential pathogenic mechanisms can explored future studies. Combined, results reveal drug targets treatment tauopathies insight into how mediates its toxicity

Язык: Английский

Процитировано

265