Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.11.17 (
CaMKII
)
4,029
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Alzheimer's disease (AD) is the disease of lost memories. Synaptic loss is a major reason for memory defects in AD. Signaling pathways involved in memory loss in AD are under intense investigation. The role of deranged neuronal calcium (Ca
2+
) signaling in synaptic loss in AD is described in this review. Familial AD (FAD) mutations in presenilins are linked directly with synaptic Ca
2+
signaling abnormalities, most likely by affecting endoplasmic reticulum (ER) Ca
2+
leak function of presenilins. Excessive ER Ca
2+
release via type 2 ryanodine receptors (RyanR2) is observed in AD spines due to increase in expression and function of RyanR2. Store-operated Ca
2+
entry (nSOC) pathway is disrupted in AD spines due to downregulation of
STIM2 protein
. Because of these Ca
2+
signaling abnormalities, a balance in activities of Ca
2+
-
calmodulin-dependent kinase II
(
CaMKII
) and Ca
2+
-dependent phosphatase calcineurin (CaN) is shifted at the synapse, tilting a balance between long-term potentiation (LTP) and long-term depression (LTD) synaptic mechanisms. As a result, synapses are weakened and eliminated in AD brains by LTD mechanism, causing memory loss. Targeting synaptic calcium signaling pathways offers opportunity for development of AD therapeutic agents.
...
PMID:Dysregulation of neuronal calcium homeostasis in Alzheimer's disease - A therapeutic opportunity? 2764 64
Store-operated calcium entry (SOCE) is one of regulatory mechanisms which regulates Ca2+ cycling in the heart. SOCE alterations in pathological conditions contribute to progression of heart failure and cardiac hypertrophy by multiple signaling pathways such as Cn/NFAT and
CaMKII
/MEF2. Several components mediating SOCE have been identified, such as STIM and Orai. Different isoforms of both Orai and STIM have been detected in animal studies, exhibiting distinct functional properties. This study is focused on the analysis of STIM and Orai isoforms expression in the end-stage human failing myocardium. Left ventricle samples isolated from 43 explanted hearts from patients undergoing heart transplant and from 5 healthy donor hearts were used to determine the mRNA levels of Orai1, Orai2 and Orai3, STIM1,
STIM2
and
STIM2
.1 by qRT-PCR. The expression was further analyzed for connection with gender, related co-morbidities, pathoetiology, clinical data and biochemical parameters. We show that Orai1 expression is decreased by 30 % in failing myocardium, even though we detected no significant changes in expression of Orai2 or Orai3. Interestingly, this decrease in Orai1 was gender-specific and was present only in men, with no change in women. The ratio Orai1/Orai3 was significantly lower in males as well. The novel
STIM2
.1 isoform was detected both in healthy and failing human myocardium. In the end-stage heart failure, the expression of
STIM2
.1 was significantly decreased. The lower ratio of
STIM2
.1/
STIM2
in failing hearts indicates a switch from SOCE-inhibiting
STIM2
.1 isoform to stimulatory
STIM2
.2. STIM1 mRNA levels were not significantly changed. These observed alterations in Orai and STIM expression were independent of functional heart parameters, clinical or biochemical patient characteristics. These results provide detailed insight into the alterations of SOCE regulation in human failing myocardium. Gender-specific change in Orai1 expression might represent a possible mechanism of cardioprotective effects of estrogens. The switch from
STIM2
.1 to
STIM2
.2 indicates an amplification of SOCE and could contribute to the hypertrophy development in the filing heart.
...
PMID:Changes in STIM isoforms expression and gender-specific alterations in Orai expression in human heart failure. 3184 80
