scholarly journals STEP inhibition prevents Aβ-mediated damage in dendritic complexity and spine density in Alzheimer’s disease.

2020 ◽  
Author(s):  
Manavi Chatterjee ◽  
Jeemin Kwon ◽  
Jessie Benedict ◽  
Marija Kamceva ◽  
Pradeep Kurup ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Mouse Model ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Spine Density ◽  
Protein Tyrosine ◽  
Dendritic Complexity ◽  
Ad Mouse Model

AbstractLoss of dendritic spines and decline of cognitive function are hallmarks of patients with Alzheimer’s disease (AD). Previous studies have shown that AD pathophysiology involves increased expression of a central nervous system-enriched protein tyrosine phosphatase called STEP (STriatal-Enriched protein tyrosine Phosphatase). STEP opposes the development of synaptic strengthening by dephosphorylating substrates, including GluN2B, Pyk2 and ERK1/2. Genetic reduction of STEP as well as pharmacological inhibition of STEP improves cognitive function and hippocampal memory in the 3xTg AD mouse model. Here, we show that the improved cognitive function is accompanied by an increase in synaptic connectivity in cell cultures as well as in the triple transgenic AD mouse model, further highlighting the potential of STEP inhibitors as a therapeutic agent.

scholarly journals Neuronal Protein Tyrosine Phosphatase 1B Hastens Amyloid β-Associated Alzheimer's Disease in Mice

2020 ◽  
Vol 40 (7) ◽  
pp. 1581-1593 ◽  
Author(s):  
Konrad M. Ricke ◽  
Shelly A. Cruz ◽  
Zhaohong Qin ◽  
Kaveh Farrokhi ◽  
Fariba Sharmin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Amyloid Β ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Neuronal Protein

scholarly journals Ambiguous Effects of Prolonged Dietary Supplementation with a Striatal-Enriched Protein Tyrosine Phosphatase Inhibitor, TC-2153, on a Rat Model of Sporadic Alzheimer’s Disease

2021 ◽  
Vol 15 (3) ◽  
pp. 292-301
Author(s):  
E. A. Rudnitskaya ◽  
A. O. Burnyasheva ◽  
T. A. Kozlova ◽  
N. A. Muraleva ◽  
D. V. Telegina ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Amyloid Β ◽  
Oxys Rats ◽  
Prolonged Treatment ◽  
Long Term Memory ◽  
Amyloid Β Protein ◽  
Protein Tyrosine

Abstract Alzheimer’s disease (AD) is the most common type of dementia and is currently incurable. After unsuccessful attempts to create drugs targeting the amyloid-β pathway, a search for alternative approaches and treatments targeting nonamyloid AD pathologies is currently underway. One of them is inhibition of striatal-enriched protein tyrosine phosphatase (STEP) activity, which is increased in the prefrontal cortex of AD patients. Here we examined effects of prolonged treatment of OXYS rats which mimic key signs of sporadic AD with a STEP inhibitor, TC-2153, on the progression of signs of AD. TC-2153 had an ambiguous effect on the behavior of the animals: it significantly reduced the already low locomotor and exploratory activities and enhanced anxiety-related behavior in OXYS rats but improved their long-term memory in the Morris water maze. Moreover, TC-2153 had no effect on the accumulation of the amyloid-β protein and on the STEP61 protein level; the latter in the cortex and hippocampus did not differ between OXYS rats and control Wistar rats. These results suggest that the effects of prolonged treatment with TC-2153 may be mediated by mechanisms not related to STEP. In particular, TC-2153 can act as a potential hydrogen sulfide donor and thus substantially affect redox homeostasis.

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