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Beschea Chiriac SI

References (2)

Title : Preclinical Studies of Canagliflozin, a Sodium-Glucose Co-Transporter 2 Inhibitor, and Donepezil Combined Therapy in Alzheimer's Disease - Stanciu_2023_Pharmaceuticals.(Basel)_16_
Author(s) : Stanciu GD , Ababei DC , Solcan C , Bild V , Ciobica A , Beschea Chiriac SI , Ciobanu LM , Tamba BI
Ref : Pharmaceuticals (Basel) , 16 : , 2023
Abstract : The incidence of neurodegenerative diseases, such as Alzheimer's disease (AD), is continuously growing worldwide, which leads to a heavy economic and societal burden. The lack of a safe and effective causal therapy in cognitive decline is an aggravating factor and requires investigations into the repurposing of commonly used drugs. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a new and efficient class of hypoglycemic drugs and, due to their pleiotropic effects, have indications that go beyond diabetes. There is emerging data from murine studies that SGLT2i can cross the blood-brain barrier and may have neuroprotective effects, such as increasing the brain-derived neurotrophic factor (BDNF), reducing the amyloid burden, inhibiting acetylcholinesterase (AChE) and restoring the circadian rhythm in the mammalian target of rapamycin (mTOR) activation. The current study investigates the effect of an SGLT2i and donepezil, under a separate or combined 21-day treatment on AD-relevant behaviors and brain pathology in mice. The SGLT2i canagliflozin was found to significantly improve the novelty preference index and the percentage of time spent in the open arms of the maze in the novel object recognition and elevated plus maze test, respectively. In addition, canagliflozin therapy decreased AChE activity, mTOR and glial fibrillary acidic protein expression. The results also recorded the acetylcholine M1 receptor in canagliflozin-treated mice compared to the scopolamine group. In the hippocampus, the SGLT2i canagliflozin reduced the microgliosis and astrogliosis in males, but not in female mice. These findings emphasize the value of SGLT2i in clinical practice. By inhibiting AChE activity, canagliflozin represents a compound that resembles AD-registered therapies in this respect, supporting the need for further evaluation in dementia clinical trials.
ESTHER : Stanciu_2023_Pharmaceuticals.(Basel)_16_
PubMedSearch : Stanciu_2023_Pharmaceuticals.(Basel)_16_
PubMedID: 38004485

Title : Alzheimer's Disease Pharmacotherapy in Relation to Cholinergic System Involvement - Stanciu_2019_Biomolecules_10_
Author(s) : Stanciu GD , Luca A , Rusu RN , Bild V , Beschea Chiriac SI , Solcan C , Bild W , Ababei DC
Ref : Biomolecules , 10 : , 2019
Abstract : Alzheimer's disease, a major and increasing global health challenge, is an irreversible, progressive form of dementia, associated with an ongoing decline of brain functioning. The etiology of this disease is not completely understood, and no safe and effective anti-Alzheimer's disease drug to prevent, stop, or reverse its evolution is currently available. Current pharmacotherapy concentrated on drugs that aimed to improve the cerebral acetylcholine levels by facilitating cholinergic neurotransmission through inhibiting cholinesterase. These compounds, recognized as cholinesterase inhibitors, offer a viable target across key sign domains of Alzheimer's disease, but have a modest influence on improving the progression of this condition. In this paper, we sought to highlight the current understanding of the cholinergic system involvement in Alzheimer's disease progression in relation to the recent status of the available cholinesterase inhibitors as effective therapeutics.
ESTHER : Stanciu_2019_Biomolecules_10_
PubMedSearch : Stanciu_2019_Biomolecules_10_
PubMedID: 31888102