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Alzheimer's disease (AD) is a multivariate and diversified disease and affects the most sensitive areas of the brain, the cerebral cortex, and the hippocampus. AD is a progressive age-related neurodegenerative disease most often associated with memory deficits and cognition that get more worsen over time. The central theory on the pathophysiological hallmark features of AD is characterized by the accumulation of amyloid β (Aβ) peptides, also associated with tau proteins (τ) dysfunctioning which leads to distorted microtubular structure, affects the cholinergic system, and mitochondrial biogenesis. This review emphasizes how simple it is to find novel treatments for AD and focuses on several recently developed medications through repurposing that can speed up traditional drug development. • Alzheimer's Disease is a multivariate and diversified disease • The cerebral cortex and hippocampus are frequently affected regions in AD. • The pathology of Alzheimer's Disease is characterized by the accumulation of β amyloid peptides and the dysfunctioning of tau proteins. • Recently developed medications through repurposing can speed up traditional drug development. [ABSTRACT FROM AUTHOR]

Parkinson's disease is a neurodegenerative illness linked to ageing, marked by the gradual decline of dopaminergic neurons in the midbrain. The exact aetiology of Parkinson's disease (PD) remains uncertain, with genetic predisposition and environmental variables playing significant roles in the disease's frequency. Epidemiological data indicates a possible connection between pesticide exposure and brain degeneration. Specific pesticides have been associated with important characteristics of Parkinson's disease, such as mitochondrial dysfunction, oxidative stress, and α-synuclein aggregation, which are crucial for the advancement of the disease. Recently, many animal models have been developed for Parkinson's disease study. Although these models do not perfectly replicate the disease's pathology, they provide valuable insights that improve our understanding of the condition and the limitations of current treatment methods. Drosophila, in particular, has been useful in studying Parkinson's disease induced by toxins or genetic factors. The review thoroughly analyses many animal models utilised in Parkinson's research, with an emphasis on issues including pesticides, genetic and epigenetic changes, proteasome failure, oxidative damage, α-synuclein inoculation, and mitochondrial dysfunction. The text highlights the important impact of pesticides on the onset of Parkinson's disease (PD) and stresses the need for more research on genetic and mechanistic alterations linked to the condition. • Pesticide exposure is a common risk factor for Parkinson's disease. • Several epidemiological investigations highlight a notable correlation between PD and pesticide exposure. • Existing animal models for PD, although valuable, do not fully replicate disease symptoms, posing challenges for research. • Drosophila's genetic composition and evolutionary robustness render it essential for investigating PD. • Discovering biomarkers for assessing past environmental exposure is crucial for managing neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

According to the facts and figures 2023stated that 6.7 million Americans over the age of 65 have Alzheimer's disease (AD). The scenario of AD has reached up to the maximum, of 4.1 million individuals, 2/3rd are female patients, and approximately 1 in 9 adults over the age of 65 have dementia with AD dementia. The fact that there are now no viable treatments for AD indicates that the underlying disease mechanisms are not fully understood. The progressive neurodegenerative disease, AD is characterized by amyloid plaques and neurofibrillary tangles (NFTs) of abnormally hyperphosphorylated tau protein and senile plaques (SPs), which are brought on by the buildup of amyloid beta (Aβ). Numerous attempts have been made to produce compounds that interfere with these characteristics because of significant research efforts into the primary pathogenic hallmark of this disorder. Here, we summarize several research that highlights interesting therapy strategies and the neuroprotective effects of GLP-1, Sigma, and, AGE-RAGE receptors in pre-clinical and clinical AD models. • Protein aggregates ,abnormal cellular activities, and disturbed inflammatory mechanisms are the major causes of AD progression. • Receptors are the potential pathogenic targets that are primarily focused by research groups nowadays to treat AD. • Inflammatory stimulus increases the secretion of GLP-1 and modulates the phenomenon of various sites of inflammation. • Neuroprotection and anti-inflammation, have been put out to account for the anti-AD actions of sigma-2 ligands. • Advanced glycation end products (AGEs) and related receptor RAGE expression is markedly high in AD patients. [ABSTRACT FROM AUTHOR]

Learning and memory storage are the fundamental activities of the brain. Aberrant expression of synaptic molecular markers has been linked to memory impairment in AD. Aging is one of the risk factors linked to gradual memory loss. It is estimated that approximately 13 million people worldwide will have AD by 2050. A massive amount of oxidative stress is kept under control by a complex network of antioxidants, which occasionally fails and results in neuronal oxidative stress. Increasing evidence suggests that ROS may affect many pathological aspects of AD, including Aβ accumulation, tau hyperphosphorylation, synaptic plasticity, and mitochondrial dysfunction, which may collectively result in neurodegeneration in the brain. Further investigation into the relationship between oxidative stress and AD may provide an avenue for effective preservation and pharmacological treatment of this neurodegenerative disease. In this review, we briefly summarize the cellular mechanism underlying Aβ induced synaptic dysfunction. Since oxidative stress is common in the elderly and may contribute to the pathogenesis of AD, we also shed light on the role of antioxidant and inflammatory pathways in oxidative stress adaptation, which has a potential therapeutic target in neurodegenerative diseases. • 4-HNE-derived pathological implications may lead to memory dysfunction. • FAB is employed as a pro-oxidant to induce oxidative stress to recreate AD. • ROS-upregulated BACE1 gene expression and Aβ production are highly correlated with AD incidence. • MFRTA suggested that aging is significantly influenced by ROS production and leads to mitophagy. • Dysfunctional UPS components affect synaptic plasticity and lead to the late phase of AD [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases (NDs) are a heterogeneous group of aging-associated ailments characterized by interrupting cellular proteostasic machinery and the misfolding of distinct proteins to form toxic aggregates in neurons. Neurodegenerative diseases, which include Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and others, are becoming an increasing threat to human health worldwide. The degeneration and death of certain specific groups of neurons are the hallmarks of these diseases. Over the past decades, Caenorhabditis elegans has beenwidely used as a transgenic model to investigate biological processes related to health and disease. The nematode Caenorhabditis elegans (C. elegans) has developed as a powerful tool for studying disease mechanisms due to its ease of genetic handling and instant cultivation while providing a whole-animal system amendable to several molecular and biochemical techniques. In this review, we elucidate the potential of C. elegans as a versatile platform for systematic dissection of the molecular basis of human disease, focusing on neurodegenerative disorders, and may help better our understanding of the disease mechanisms and search for new therapeutics for these devastating diseases. • The interruption of cellular proteostasic machinery characterizes neurodegenerative diseases. • The degeneration and death of certain specific groups of neurons are the hallmarks of these diseases. • C. elegans has developed as a powerful tool for studying neurodegenerative disease mechanisms. • C. elegans provides a whole-animal system amendable to several molecular and biochemical techniques. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is characterized by an adverse cellular environment and pathological alterations in distinct brain regions. The development is triggered or facilitated by a condition such as hypoxia or ischemia, or inflammation and is associated with disruptions of fundamental cellular functions, including metabolic and ion homeostasis. Increasing evidence suggests that hypoxia may affect many pathological aspects of AD, including oxidative stress, mitochondrial dysfunction, ER stress, amyloidogenic processing of APP, and Aβ accumulation, which may collectively result in neurodegeneration. Further investigation into the relationship between hypoxia and AD may provide an avenue for the effective preservation and pharmacological treatment of this neurodegenerative disease. This review summarizes the effects of normoxia and hypoxia on AD pathogenesis and discusses the underlying mechanisms. Regulation of HIF-1α and the role of its key players, including P53, VEGF, and GLUT1, are also discussed. • Hypoxia is one detrimental aspect of ischemia and stroke and also leads to AD development. • Hypoxia leads to Mitophagy and ER stress, which ultimately increase the chances of AD. • HIF-1 is known to maintained oxygen homeostasis, cellular energy metabolism, and tumor expression. • HIF-1α has been elucidated the representative transcription factor of hypoxic condition. • Signalling pathways plays a vital role in the induction of endogenous anti-oxidant enzymes against oxidative stress. [ABSTRACT FROM AUTHOR]