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: UMLS:C0751295 (
memory loss
)
3,619
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The precise molecular and cellular events responsible for age-dependent cognitive dysfunctions remain unclear. We report that
Rheb
(ras homolog enriched in brain) GTPase, an activator of mammalian target of rapamycin (mTOR), regulates memory functions in mice. Conditional depletion of
Rheb
selectively in the forebrain of mice obtained from crossing
Rheb
f/f
and CamKII
Cre
results in spontaneous signs of age-related
memory loss
, that is, spatial memory deficits (T-maze, Morris water maze) without affecting locomotor (open-field test), anxiety-like (elevated plus maze), or contextual fear conditioning functions. Partial depletion of
Rheb
in forebrain was sufficient to elicit memory defects with little effect on the neuronal size, cortical thickness, or mammalian target of rapamycin activity.
Rheb
depletion, however, increased the levels of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), a protein elevated in aging and Alzheimer's disease. Overall, our study demonstrates that forebrain
Rheb
promotes aging-associated cognitive defects. Thus, molecular understanding of
Rheb
pathway in brain may provide new therapeutic targets for aging and/or Alzheimer's disease-associated memory deficits.
...
PMID:Forebrain depletion of Rheb GTPase elicits spatial memory deficits in mice. 2796 Jan 7
