Alzheimer-related pathogenesis is dependent on neuronal receptor PTPσ.
Gu, Y.; Shu, Y.; Corona, A.; Xu, K.; Yi, A. F.; Chen, S.; Luo, M.; Tremblay, M.; Landreth, G. E.; Nelson, R.; Silver, J.; Shen, Y.
Show abstract
Due to limited understanding of disease mechanisms and the lack of molecular targets, translational research for Alzheimer disease has not been fruitful hitherto. Here we report findings that indicate neuronal receptor phosphatase PTP{sigma} as a potential therapeutic target for this dementia. In two TgAPP mouse models, a spectrum of Alzheimer-related pathologies, including aged-induced progression of {beta}-amyloidosis, Tau aggregation, neuroinflammation, synaptic loss, as well as behavioral deficits, all show unambiguous dependency on PTP{sigma}. APP amyloidogenic metabolites diminish upon PTP{sigma} genetic depletion or pharmacological inhibition. Binding to APP in the brain, PTP{sigma} regulates APP proteolytic metabolism via its phosphatase activity, likely through downstream signaling that modulates APP membrane localization and affinity to the {beta}-secretase, in a specific manner that does not broadly affect {beta}- and {gamma}-secretase processing of other major substrates. Together, these findings unveil a gatekeeping role of PTP{sigma} upstream in Alzheimer-like pathogenic pathway.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Aβ42 oligomers trigger synaptic loss through CAMKK2-AMPK-dependent effectors coordinating mitochondrial fission and mitophagy 95%
- Identification of Chlamydia pneumoniae and NLRP3 inflammasome activation in Alzheimer's disease retina 95%
- TFEB degradation is regulated by an IKK/β-TrCP2 phosphorylation-ubiquitination cascade 95%
Similar papers in this journal
- Lysosomal dysfunction in Down Syndrome and Alzheimer mouse models is caused by selective v-ATPase inhibition by Tyr682 phosphorylated APP βCTF 96%
- Single-synapse analyses of Alzheimers disease implicate pathologic tau, DJ1, CD47, and ApoE 95%
- Numb reduces Tau levels and prevents neurodegeneration in mouse models of tauopathy in an isoform-specific manner 94%
Similar papers in this journal
- APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology 96%
- β-Amyloid Induces Microglial Expression of GPC4 and APOE Leading to Increased Neuronal Tau Pathology and Toxicity 95%
- A Trem2*R47H mouse model without cryptic splicing drives age- and disease-dependent tissue damage and synaptic loss in response to plaques 95%
Similar papers in this journal
- Aβ-driven nuclear pore complex dysfunction alters activation of necroptosis proteins in a mouse model of Alzheimer's Disease 95%
- Downregulation of Dickkopf-3, a Wnt antagonist elevated in Alzheimer's disease, restores synapse integrity and memory in a disease mouse model 95%
- Sleep is bi-directionally modified by amyloid beta oligomers 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.