الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
There are currently 35.6 million people living with dementia globally, and 7.7
million new cases are identified each year. As the most frequent cause of dementia,
Alzheimer’s disease (AD) accounts for 60–75% of all cases. Additionally, whereas
mortality from other illnesses, such heart disease, have declined recently, those linked to
AD have climbed by 68% in just the past ten years. Age is the primary risk factor in the
etiopathogenesis of AD, and as life expectancy rises, so does the prevalence of the disease.
A prominent impairment of episodic memory is a hallmark of AD. This symptom is
frequently accompanied by a wide range of cognitive deficits in areas like decisionmaking,
language, executive function, and visuospatial skills. As a result, AD seems to be
a gradual decline in higher brain functioning that also affects judgement. Patients with
Alzheimer’s live an average of 7 to 10 years after diagnosis. Further complicating early
diagnosis and therapy is the lack of a clear premortem diagnosis for this illness, which can
only be determined histologically postmortem by the presence of senile plaques (SPs),
neurofibrillary tangles (NFTs) and neuronal and synaptic loss.
There is still no effective treatment to stop or reduce the development of AD, despite
the rise in cases in recent years and the associated socioeconomic costs. Only six
medications, including aducanumab, donepezil, galantamine, rivastigmine, memantine, and
a manufactured combination of memantine and donepezil (DP), have received food and
drug administration (FDA) approval thus far. Only aducanumab is used to remove amyloid
beta (Aβ) plaques; the other five are symptomatic treatments that work on two levels,
either by antagonizing the cholinergic system or by blocking the N-methyl-D-aspartate
receptor (NMDA-receptor). Due to side effects that are associated with these drugs
especially nausea, vomiting and headache, it was a necessary to search for less side effects
drugs such as natural products. An exceptional unique bioflavonoid called quercetin (QCT)
is strictly recommended due to numerous therapeutic effects which have been documented
including antioxidant, anti-inflammatory, anti-amyloidogenic, and neuroprotective effects.
Summary and Conclusion
131
This study aimed to evaluate the neurotherapeutic effect of QCT on the expression of
miR-124 in experimental AD model and to compare the efficiency of QCT to
conventionally used drug; DP. The study was conducted on 40 healthy male albino rats
weighted approximately 100-150 g and divided into two groups: Normal control group
(GI; n=8) received standard diet, and AD group (GII; n=32) that received hydrated
aluminum chloride (AlCl3.6H2O) solution that was given orally at a dose of 75 mg/kg/day
for 6 weeks, subdivided into 4 subgroups (8 rats each): GII A: untreated Alzheimer rats;
GII B: AD rats received QCT interperitoneally with a dose of 30 mg/kg/day for 4 weeks.
GII C: AD rats received DP orally with a dose of 3 mg/kg/day for 4 weeks.; GII D: AD rats
received a daily dose of the combination of QCT and DP for 4 weeks.
The results of the present study indicated that untreated rats have a significantly
higher Aβ1-42 contents, hyperphosphorylated tau proteins, malondialdehyde (MDA)
contents, AChE activity and nuclear factor kappa B (NF-κB) contents as compared to
control rats. Also, AD rats showed a significant upregulation of BACE1 gene expression
and a significant suppression in miR-124 expression. from the results of the present study,
it is clear that the hippocampal Aβ1-42 level and tau protein content were completely
normalized in AD-like rats treated with QCT in combination with DP. In addition to
previous results, the best ameliorating effect on AChE activity was observed in AD rats
treated with the combined treatment regimen. In hippocampus, the treatment with DP alone
or QCT alone or combined with DP significantly downregulate the expression of BACE1
and upregulate miR-124 expression compared with the untreated rats. These results
suggested that the best effects were obtained in the combined treatment regimen.
The biochemical results of the current study were further confirmed by the
histological examination of the hippocampus tissues. The normal group revealed an intact
architecture of the hippocampus with normal histological appearance. The hippocampus
of AD rats showed degenerative changes and atrophy of the neuronal cells.
Administration of QCT and DP resulted in marked improvement of cellular morphology
to various extents as compared to the untreated rats, improvement of nerve cell
morphology, decline in numbers of degenerated, pyknotic neurons, necrotic neurons
associated with satellitosis and neuronophagia and result in significant reduction of optical
density and also reduction of Aβ deposition.
Summary and Conclusion
132
from the results obtained it can be concluded that:
Quercetin is considered as a potential therapeutic agent against Alzheimer’s disease.
• QCT targets multiple pathways involved in AD progression including induced
amyloidogenic pathway, impaired cholinergic neurotransmission, oxidative stress,
upregulation of BACE1 gene expression and downregulation of miR-124 gene
expression in hippocampal tissues and enhancing the diseased AD-rats cognitive
function.
• from histological observation, the best results were observed in the hippocampus of
animals that received the combination of QCT and DP. These observations indicated
that the treatment mitigated the AD histopathological alterations in the hippocampus of
AD rats and improve the morphology and distribution of nerve cells.
• According to the results achieved here, we recommend the use of QCT as adjuvant
therapy with DP for treatment of AD.
• Further studies are required to investigate the therapeutic and protective effects of QCT
in AD patients and the actual mechanism behind these effects and investigate the role of
miRNAs in AD progression.