Neurodegenerative diseases (NDDs) are the primary cause of disabilities in the elderly people. Growing evidence indicates that oxidative stress, mitochondrial dysfunction, neuroinflammation and apoptosis are associated with aging and the basis of most neurodegenerative disorders. Quercetin is a flavonoid with significant pharmacological effects and promising therapeutic potential. It is widely distributed among plants and typically found in daily diets mainly in fruits and vegetables. It shows a number of biological properties connected to its antioxidant activity. Neuroprotection by quercetin has been reported in many in vitro as well as in in vivo studies. However, the exact mechanism of action is still mystery and similarly there are a number of hypothesis exploring the mechanism of neuroprotection. Quercetin enhances neuronal longevity and neurogenesis by modulating and inhibiting wide number of pathways. This review assesses the food sources of quercetin, its pharmacokinetic profile, structure activity relationship and its pathophysiological role in various NDDs and it also provides a synopsis of the literature exploring the relationship between quercetin and various downstream signalling pathways modulated by quercetin for neuroprotection for eg. nuclear factor erythroid 2-related factor 2 (Nrf2), Paraoxonase-2 (PON2), c-Jun N-terminal kinase (JNK), Tumour Necrosis Factor alpha (TNF-α), Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha (PGC-1α), Sirtuins, Mitogen-activated protein kinases (MAPKs) signalling cascades, CREB (Cyclic AMP response element binding protein) and Phosphoinositide 3- kinase(PI3K/Akt). Therefore, the aim of the present review was to elaborate on the cellular and molecular mechanisms of the quercetin involved in the protection against NDDs.

The ubiquitin-proteasome pathway (UPP) is involved in regulating several biological functions, including cell cycle control, apoptosis, DNA damage response, and apoptosis. It is widely known for its role in degrading abnormal protein substrates and maintaining physiological body functions via ubiquitinating enzymes (E1, E2, E3) and the proteasome. Therefore, aberrant expression in these enzymes results in an altered biological process, including transduction signaling for cell death and survival, resulting in cancer. In this review, an overview of profuse enzymes involved as a pro-oncogenic or progressive growth factor in tumors with their downstream signaling pathways has been discussed. A systematic literature review of PubMed, Medline, Bentham, Scopus, and EMBASE (Elsevier) databases was carried out to understand the nature of the extensive work done on modulation of ubiquitin-proteasome pathways in oncogenic signaling. Various in vitro, in vivo studies demonstrating the involvement of ubiquitin-proteasome systems in varied types of cancers and the downstream signaling pathways involved are also discussed in the current review. Several inhibitors of E1, E2, E3, deubiquitinase enzymes and proteasome have been applied for treating cancer. Some of these drugs have exhibited successful outcomes in in vivo studies on different cancer types, so clinical trials are going on for these inhibitors. This review mainly focuses on certain ubiquitin-proteasome enzymes involved in developing cancers and certain enzymes that can be targeted to treat cancer.

Alzheimer’s disease is an ailment that is linked with the degeneration of the brain cells, and this illness is the main cause of dementia. Metabolic stress affects the activity of the brain in AD via FOXO signaling. The occurrence of AD will significantly surge as the world’s population ages, along with lifestyle changes perceived in current decades, indicating a main contributor to such augmented prevalence. Similarly, metabolic disorders of current adulthood, such as obesity, stroke, and diabetes mellitus, have been observed as the risk-causing factors of AD. Environmental influences induce genetic mutations that result in the development of several diseases. Metabolic disorders develop when individuals are exposed to an environment where food is easily accessible and requires minimal energy expenditure. Obesity and diabetes are among the most significant worldwide health concerns. Obesity arises because of an imbalance between the amount of energy consumed and the amount of energy expended, which is caused by both behavioral and physiological factors. Obesity, insulin resistance syndrome, hypertension, and inflammation are factors that contribute to the worldwide risk of developing diabetes mellitus and neurodegenerative diseases. FOXO transcription factors are preserved molecules that play an important part in assorted biological progressions, precisely in aging as well as metabolism. Apoptosis, cell division and differentiation, oxidative stress, metabolism, and lifespan are among the physiological processes that the FOXO proteins are adept at controlling. In this review, we explored the correlation between signaling pathways and the cellular functions of FOXO proteins. We have also summarized the intricate role of FOXO in AD, with a focus on metabolic stress, and discussed the prospect of FOXO as a molecular link between AD and metabolic disorders.