PMC:4718081 / 2693-4767
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4718081","sourcedb":"PMC","sourceid":"4718081","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4718081","text":"AD has two major pathological hallmarks in CSF including senile plaques and neurofibrillary tangles (NFT) (Kimura et al., 2014). NFTs make up from intracellular aggregates of hyperphosphorylated tau protein (P-tau) and senile plaques consist mainly of amyloid β peptide (Aβ) (Small, 2008; Kimura et al., 2014). Previous researches have shown the interaction of tau, P-tau, and Aβ (Figure 1). On one hand, P-tau can increase activity of acetyl-cholinesterase (AChE). Then the increased AChE activity can elevate Aβ production by modulating the levels of the γ-secretase catalytic subunit presenilin-1 (PS1) (García-Ayllón et al., 2011). On the other hand, Aβ may affect the level of P-tau through two pathways. Firstly, Aβ can raise the activity of AChE which can activate the tau kinase glycogen synthase kinase-3β (GSK-3β) inducing tau hyperphosphorylation (García-Ayllón et al., 2011). Secondly, Aβ can activate the voltage-dependent Ca2+ channels (VVCD) and N-methyl-D-aspartic acid (NMDA) receptors which results in the release of intracellular Ca2+ (Shen et al., 2006; Bezprozvanny and Mattson, 2008). Then the increased levels of intracellular Ca2+ might initiate a signal transduction pathway to activate Ca2+-sensitive protein kinases which are responsible for the hyperphosphorylation of tau (Shen et al., 2006). Furthermore, previous researches have expounded the role of Aβ and tau pathology. On one hand, Aβ plays a vital role in progression of AD which may lead in turn to a series of downstream events ranging from synapse loss to plaque deposition to inflammation to the triggering of tau hyperphosphorylation to the death of susceptible neurons (Herrup, 2010). On the other hand, tau pathology plays a complicated role in the progression of AD. Tau pathology may affect DNA repair, neuronal activity, and inter-neuronal signaling (Hanger et al., 2014). Though the mechanism and roles of tau pathology are not yet fully elucidated, a consensus that the tau pathology can enhance cognitive decline and cause dementia is widely accepted (Salminen et al., 2011).","tracks":[{"project":"TEST0","denotations":[{"id":"26834548-122-130-278832","span":{"begin":122,"end":126},"obj":"[\"25076872\"]"},{"id":"26834548-154-162-278833","span":{"begin":283,"end":287},"obj":"[\"18262842\"]"},{"id":"26834548-175-183-278834","span":{"begin":304,"end":308},"obj":"[\"25076872\"]"},{"id":"26834548-163-171-278835","span":{"begin":629,"end":633},"obj":"[\"21949503\"]"},{"id":"26834548-171-179-278836","span":{"begin":881,"end":885},"obj":"[\"21949503\"]"},{"id":"26834548-180-188-278837","span":{"begin":1068,"end":1072},"obj":"[\"17055782\"]"},{"id":"26834548-212-220-278838","span":{"begin":1100,"end":1104},"obj":"[\"18675468\"]"},{"id":"26834548-208-216-278839","span":{"begin":1315,"end":1319},"obj":"[\"17055782\"]"},{"id":"26834548-231-239-278840","span":{"begin":1670,"end":1674},"obj":"[\"21159946\"]"},{"id":"26834548-101-109-278841","span":{"begin":1862,"end":1866},"obj":"[\"24595196\"]"},{"id":"26834548-199-207-278842","span":{"begin":2068,"end":2072},"obj":"[\"21056617\"]"}],"attributes":[{"subj":"26834548-122-130-278832","pred":"source","obj":"TEST0"},{"subj":"26834548-154-162-278833","pred":"source","obj":"TEST0"},{"subj":"26834548-175-183-278834","pred":"source","obj":"TEST0"},{"subj":"26834548-163-171-278835","pred":"source","obj":"TEST0"},{"subj":"26834548-171-179-278836","pred":"source","obj":"TEST0"},{"subj":"26834548-180-188-278837","pred":"source","obj":"TEST0"},{"subj":"26834548-212-220-278838","pred":"source","obj":"TEST0"},{"subj":"26834548-208-216-278839","pred":"source","obj":"TEST0"},{"subj":"26834548-231-239-278840","pred":"source","obj":"TEST0"},{"subj":"26834548-101-109-278841","pred":"source","obj":"TEST0"},{"subj":"26834548-199-207-278842","pred":"source","obj":"TEST0"}]},{"project":"0_colil","denotations":[{"id":"26834548-25076872-278832","span":{"begin":122,"end":126},"obj":"25076872"},{"id":"26834548-18262842-278833","span":{"begin":283,"end":287},"obj":"18262842"},{"id":"26834548-25076872-278834","span":{"begin":304,"end":308},"obj":"25076872"},{"id":"26834548-21949503-278835","span":{"begin":629,"end":633},"obj":"21949503"},{"id":"26834548-21949503-278836","span":{"begin":881,"end":885},"obj":"21949503"},{"id":"26834548-17055782-278837","span":{"begin":1068,"end":1072},"obj":"17055782"},{"id":"26834548-18675468-278838","span":{"begin":1100,"end":1104},"obj":"18675468"},{"id":"26834548-17055782-278839","span":{"begin":1315,"end":1319},"obj":"17055782"},{"id":"26834548-21159946-278840","span":{"begin":1670,"end":1674},"obj":"21159946"},{"id":"26834548-24595196-278841","span":{"begin":1862,"end":1866},"obj":"24595196"},{"id":"26834548-21056617-278842","span":{"begin":2068,"end":2072},"obj":"21056617"}],"attributes":[{"subj":"26834548-25076872-278832","pred":"source","obj":"0_colil"},{"subj":"26834548-18262842-278833","pred":"source","obj":"0_colil"},{"subj":"26834548-25076872-278834","pred":"source","obj":"0_colil"},{"subj":"26834548-21949503-278835","pred":"source","obj":"0_colil"},{"subj":"26834548-21949503-278836","pred":"source","obj":"0_colil"},{"subj":"26834548-17055782-278837","pred":"source","obj":"0_colil"},{"subj":"26834548-18675468-278838","pred":"source","obj":"0_colil"},{"subj":"26834548-17055782-278839","pred":"source","obj":"0_colil"},{"subj":"26834548-21159946-278840","pred":"source","obj":"0_colil"},{"subj":"26834548-24595196-278841","pred":"source","obj":"0_colil"},{"subj":"26834548-21056617-278842","pred":"source","obj":"0_colil"}]},{"project":"2_test","denotations":[{"id":"26834548-25076872-38218422","span":{"begin":122,"end":126},"obj":"25076872"},{"id":"26834548-18262842-38218423","span":{"begin":283,"end":287},"obj":"18262842"},{"id":"26834548-25076872-38218424","span":{"begin":304,"end":308},"obj":"25076872"},{"id":"26834548-21949503-38218425","span":{"begin":629,"end":633},"obj":"21949503"},{"id":"26834548-21949503-38218426","span":{"begin":881,"end":885},"obj":"21949503"},{"id":"26834548-17055782-38218427","span":{"begin":1068,"end":1072},"obj":"17055782"},{"id":"26834548-18675468-38218428","span":{"begin":1100,"end":1104},"obj":"18675468"},{"id":"26834548-17055782-38218429","span":{"begin":1315,"end":1319},"obj":"17055782"},{"id":"26834548-21159946-38218430","span":{"begin":1670,"end":1674},"obj":"21159946"},{"id":"26834548-24595196-38218431","span":{"begin":1862,"end":1866},"obj":"24595196"},{"id":"26834548-21056617-38218432","span":{"begin":2068,"end":2072},"obj":"21056617"}],"attributes":[{"subj":"26834548-25076872-38218422","pred":"source","obj":"2_test"},{"subj":"26834548-18262842-38218423","pred":"source","obj":"2_test"},{"subj":"26834548-25076872-38218424","pred":"source","obj":"2_test"},{"subj":"26834548-21949503-38218425","pred":"source","obj":"2_test"},{"subj":"26834548-21949503-38218426","pred":"source","obj":"2_test"},{"subj":"26834548-17055782-38218427","pred":"source","obj":"2_test"},{"subj":"26834548-18675468-38218428","pred":"source","obj":"2_test"},{"subj":"26834548-17055782-38218429","pred":"source","obj":"2_t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