Genetic and environmental risk factors of Parkinsonism

Genetics of α-Synuclein: The Prime Pathological Player of Parkinson’s Disease

Environmental determinants of neurotoxicity: role of heavy metals in neurological disorders

Neurodevelopmental and neurodegenerative disorders are related disorders lying on a spectrum of neural dysfunction with overlapping molecular and cellular mechanisms. Early-life diseases like autism spectrum disorder and attention-deficit/hyperactivity disorder are the result of disturbed neurodevelopment, while late-onset diseases such as Alzheimer’s disease and Parkinson’s disease are defined by progressive neuronal loss and loss of function. Emerging evidence shows that environmental exposures are important, modifiable factors that affect brain health throughout the lifespan. Factors such as air pollution, heavy metals, pesticides, and endocrine-disrupting chemicals act in combination with genetic susceptibility to disrupt neurogenesis, synaptic plasticity, and neuro-immune signaling. These exposures cause persistent epigenetic modifications, oxidative stress, mitochondrial dysfunction, and chronic neuro-inflammation, linking early developmental insults to neurodegenerative processes later in life. The concepts of the exposome and the developmental origins of health and disease provide additional support for the cumulative, lifelong impact of environmental interactions. Mechanistically, the recurrent process of neuronal damage is caused by impaired proteostasis, microglial stimulation, and blood–brain barrier dysfunction. Furthermore, the gut-brain axis is a hyperactive system in which immune responses and microbial metabolites trigger neurobiological responses to external stimuli. This review integrates multidisciplinary evidence to elucidate the mechanism and emphasizes environmental risk mitigation and translational strategies to reduce disease burden and promote lifelong brain resilience.

Exploring shared genetic pathways and gene interplay in major neurodegenerative diseases: a comprehensive review.

This review examines the common genetic pathways, along with the interactions between genes of major neurodegenerative diseases, with a focus on the key genes, such as APOE, SNCA, MAPT, TARDBP, LRRK2 and HTT.

The molecular and genetic view of tauopathies: From structural polymorphism to systemic neurodegeneration

Tauopathies constitute a broad group of clinically heterogeneous neurodegenerative disorders, including Alzheimer’s disease, progressive supranuclear palsy, and Pick’s disease, characterized by abnormal metabolism, misfolding, and intracellular aggregation of the microtubule-associated protein tau. These diseases are defined by disruptions in alternative splicing of the tau protein, toxic post-translational modifications such as hyperphosphorylation and acetylation, and the “prion-like” spread of pathological tau seeds across anatomically connected regions. Recent cryogenic electron microscopy studies have demonstrated that each tauopathy has a unique filament-folding structure, elucidating the molecular basis of phenotypic variation among diseases. The aim of this review is to provide a holistic perspective by synthesizing recent developments in the molecular and genetic architecture of tauopathies, particularly newly discovered genetic risk loci and cellular proteostasis mechanisms. In this context, detailing the process from the physiological functions of the tau protein to its pathological transformation aims to analytically evaluate the diagnostic value of fluid biomarkers and current data on next-generation clinical-stage therapeutic strategies, such as monoclonal antibodies and antisense oligonucleotides.

Neurons to Genes A Comprehensive Review of Parkinson’s Disease

The urgent need for reliable biomarkers, early diagnosis, and multidisciplinary disease-modifying strategies for future therapeutic interventions is highlighted, with particular emphasis on challenges associated with bench-to-bedside translation.

Chronic Paraquat Neurotoxicity and Dopaminergic Degeneration: A Mechanistic Review

ABSTRACT Parkinson's disease (PD) is a significant neurodegenerative disorder that affects 1%–2% of the entire global population. Despite its higher prevalence, an effective treatment that prevents or reverses neuronal damage is still not available. Clinical characteristics of PD include bradykinesia, postural instability, tremor, and rigidity. This disease is pathologically defined by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and by Lewy pathology with aggregated α‐synuclein (oligomers), although the exact role of Lewy bodies (LB) in cell death is controversial. Like other neurodegenerative disorders, the etiology of PD is associated with genetic, environmental, and other unknown factors. Certain neurotoxins such as rotenone, maneb, 6‐OHDA, MPTP and paraquat are main factors in the causation of PD. Among them, paraquat (PQ) is strongly linked with PD because of its common use in developing countries. Many in vitro and in vivo studies have reported the occurrence of PD due to exposure to PQ. The apoptotic cell death caused by PQ is associated with oxidative stress, ER stress, catabolic changes in dopamine, mitochondrial dysfunction, and so forth. The current review will summarize the available scientific evidence concerning the use and impacts of chronic exposure to PQ in the light of PD.