Action Mechanisms of Curcumin in Alzheimer’s Disease and Its Brain Targeted Delivery

Abstract

AD is a chronic neurodegenerative disease. Many different signaling pathways, such as Wnt/β-catenin, Notch, ROS/JNK, and PI3K/Akt/mTOR are involved in Alzheimer’s disease and crosstalk between themselves. A promising treatment involves the uses of flavonoids, and one of the most promising is curcumin; however, because it has difficulty permeating the blood–brain barrier (BBB), it must be encapsulated by a drug carrier. Some of the most frequently studied are lipid nanocarriers, liposomes, micelles and PLGA. These carriers are further conjugated with brain-targeting agents such as lactoferrin and transferrin. In this review paper, curcumin and its therapeutic effects, which have been examined in vivo, are analyzed and then the delivery systems to the brain are addressed. Overall, the analysis of the literature revealed great potential for curcumin in treating AD and indicated the challenges that require further research.

Protective Effect of Natural Antioxidant, Curcumin Nanoparticles, and Zinc Oxide Nanoparticles against Type 2 Diabetes-Promoted Hippocampal Neurotoxicity in Rats

“…In addition, curcumin attenuated the oxidative stress in a streptozotocin (STZ)-induced model by enhancing reduced glutathione (GSH) content and reducing the acetylcholinesterase activity in the hippocampus and cerebral cortex [22,23]. Previous studies showed that curcumin increased lifespan and decreased amyloid neurotoxicity in an invertebrate model [24,25].…”

The Interplay of the Unfolded Protein Response in Neurodegenerative Diseases: A Therapeutic Role of Curcumin

“…Curcumin, however, has certain disadvantages too, which includes its low water solubility and bioavailability. Dissolving it into organic solvent improves it solubility but its absorption remains poor (Ege, 2021;Jia et al, 2021). Some recent articles addressed the methods to enhance curcumin's effectiveness in treating AD (Fan et al, 2018;Francesco et al, 2019;Ege, 2021).…”

“…Dissolving it into organic solvent improves it solubility but its absorption remains poor (Ege, 2021;Jia et al, 2021). Some recent articles addressed the methods to enhance curcumin's effectiveness in treating AD (Fan et al, 2018;Francesco et al, 2019;Ege, 2021). In future curcumin compounds must be chemically screened on target enzymes and proteins to facilitate more information.…”

“…Curcumin further helps in inhibition of neuroinflammation possibly by binding to the sensile plaques, inhibiting Aβ plaque aggregation, plaque pathology, and decreasing amyloid levels (Lim et al, 2001;McClure et al, 2017;Mei et al, 2020). It also inhibits several dysregulated cellsignaling pathways (Su et al, 2020;Ege, 2021). Curcumin also safeguards against AD (Desai and Patravale, 2018;Nebrisi et al, 2020).…”

Development and in vivo Evaluation of Hydroxy-α-Sanshool Intranasal Liposomes as a Potential Remedial Treatment for Alzheimer’s Disease

“…A previous study suggested that the clinical symptoms of AD are divided into memory and cognitive impairments, accompanied by reduced self-care ability and abnormal mental manifestations while its aetiology and pathogenesis are still not fully understood. 2,3 Furthermore, the pathological features of AD are the presence of senile plaques and neurofibrillary tangles in the brain, while its proposed pathogenic mechanisms mainly include cholinergic dysfunction, the tau protein hyperphosphorylation hypothesis, the Aβ cascade hypothesis and the oxidative stress hypothesis. [4][5][6] Nevertheless, the current drug pipeline for AD in clinical trials remains dry, as cholinesterase inhibitors and glutamate receptor antagonists only ameliorate symptoms and do not cure the disease.…”