Alzheimer’s disease (AD) is the most common form of dementia. The pathological hallmarks of AD are amyloid plaques [aggregates of amyloid-beta (Aβ)] and neurofibrillary tangles (aggregates of tau). Growing evidence suggests that tau accumulation is pathologically more relevant to the development of neurodegeneration and cognitive decline in AD patients than Aβplaques. Oxidative stress is a prominent early event in the pathogenesis of AD and is therefore believed to contribute to tau hyperphosphorylation. Several studies have shown that the autophagic pathway in neurons is important under physiological and pathological conditions. Therefore, this pathway plays a crucial role for the degradation of endogenous soluble tau. However, the relationship between oxidative stress, tau protein hyperphosphorylation, autophagy dysregulation, and neuronal cell death in AD remains unclear. Here, we review the latest progress in AD, with a special emphasis on oxidative stress, tau hyperphosphorylation, and autophagy. We also discuss the relationship of these three factors in AD.

Parkinson's disease (PD), a complex neurodegenerative disorder characterized by selective loss of substantia nigra (SN) dopaminergic neurons, pathological aggregation of α-synuclein (α-syn), and chronic neuroinflammation, is fundamentally driven by redox imbalance and oxidative stress. Recent studies reveal that a dynamic interplay of programmed and non-programmed cell death mechanisms-amplified by oxidative damage-drives PD progression. Programmed cell death pathways include apoptosis (caspase-dependent mitochondrial/extrinsic pathways), necroptosis (eceptor-interacting serine/threonine-protein kinase 1 (RIPK1)/RIPK3/mixed lineage kinase domain-like protein (MLKL) axis), pyroptosis (NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome/Gasdermin D (GSDMD)-mediated pore formation), PARthanatos (DNA damage-poly ADP-ribose polymerase (PARP-1)/apoptosis-inducing factor (AIF) cascade), ferroptosis (redox imbalance-driven lipid peroxidation/glutathione peroxidase 4 (GPX4) inactivation), disulfidptosis (disulfide stress from cystine metabolic collapse), and cuproptosis (mitochondrial lipoylated protein toxicity via copper-mediated oxidative damage), while non-programmed necrosis is triggered by energy collapse and calcium overload. Mitochondrial dysfunction, endoplasmic reticulum stress (ERS), and oxidative stress act as central redox hubs, integrating multiple death pathways through reactive oxygen species (ROS) bursts (O₂·^-, H₂O₂, ·OH), calcium dysregulation, and metabolic abnormalities, forming a self-amplifying vicious cycle. Non-neuronal cells (e.g., microglia and astrocytes) exacerbate neuronal redox damage by releasing pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β)), dysregulating iron/copper metabolism (enhancing Fenton chemistry), and suppressing autophagic flux. Therapeutic strategies targeting redox-critical nodes include caspase/RIPK1 inhibition, GPX4 activators, autophagy modulators (rapamycin), acid β-glucocerebrosidase (GBA1) restoration, iron/copper chelators, and antioxidants (N-acetylcysteine) to restore glutathione homeostasis. Additionally, regulating glial polarization (triggering receptor expressed on myeloid cells 2 (TREM2) agonists) may disrupt inflammation-redox-death loops. Future challenges include deciphering spatiotemporal heterogeneity of cell death, developing multi-target redox therapies, and advancing biomarker-driven precision medicine (circulating free DNA (cfDNA), p-MLKL). Targeting redox dysregulation will guide breakthrough PD therapies.

In Parkinson's disease (PD), neurotoxic microglia, Th1 cells, and Th17 cells are overactivated. Overactivation of these immune cells exacerbates the disease process and leads to the pathological development of pro-inflammatory cytokines, chemokines, and contact-killing compounds, causing the loss of dopaminergic neurons. So far, we have mainly focused on the role of the specific class of immune cells in PD while neglecting the impact of interactions among immune cells on the disease. Therefore, this review demonstrates the reciprocal interplays between microglia and T cells and the associated subpopulations through cytokine and chemokine production that impair and/or protect the pathological process of PD. Furthermore, potential targets and models of PD neuroinflammation are highlighted to provide the new ideas/directions for future research.

Background: Exercises are an effective treatment in Parkinson’s disease (PD), but there is still controversy over which types should be used. We aimed to compare and rank the types of exercise that improve PD symptoms by quantifying information from randomised controlled trials. Methods: We performed a systematic review and network meta-analysis and searched PubMed, MEDLINE, Embase, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and China National Knowledge Infrastructure (CNKI) from their inception date to June 30, 2022. We included randomized controlled trials of 24 types of exercise for the interventional treatment of adults (≥ 50 years old) with PD. Effect size measures were standardized mean differences (SMDs) with 95% credible intervals (CrIs). The confidence of evidence was examined using Confidence in Network Meta-Analysis (CINeMA). Results: We identified 10 474 citations and included 250 studies involving 13 011 participants. Results of NMA showed that power training (PT) had the best benefits for motor symptoms compared with the control group (CON), with SMDs (95% CrI) (-1.46, [-2.18 to -0.74]). Body weight support treadmill training (BWS_TT) showed the best improvement in balance (1.55, [0.72 to 2.37]), gait velocity (1.15 [0.57 to 1.31]) and walking distance (1.96, [1.18 to 2.73]), and robotic assisted gait training (RA_GT) had the most benefits for freezing of gait (-1.09, [-1.80 to -0.38]). For non-motor symptoms, Dance showed the best benefits for depression (-1.71, [-2.79 to -0.73]). Only Yoga significantly reduced anxiety symptom compared with CON (-0.53, [0.96 to -0.11]). Only resistance training (RT) significantly enhanced sleep quality and cognition (-1.42, [-2.60 to -0.23]; 0.51, [0.09 to 0.94]). For muscle strength, PT showed the best advance (1.04, [0.64 to 1.44]). For concern of falling, five types of exercise were more effective than CON. Conclusions: There is low quality evidence that PT, Yoga, BWS_TT, Dance, and RT are the most effective treatments, pending outcome of interest, for adults with PD. Trial registration: PROSPERO (CRD42021220052).

Cellular senescence and chronic inflammation in response to aging are considered to be indicators of brain aging; they have a great impact on the aging process and are the main risk factors for neurodegeneration. Reviewing the microglial response to aging and neuroinflammation in neurodegenerative diseases will help understand the importance of microglia in neurodegenerative diseases. This review describes the origin and function of microglia and focuses on the role of different states of the microglial response to aging and chronic inflammation on the occurrence and development of neurodegenerative diseases, including Alzheimer’s disease, Huntington’s chorea, and Parkinson’s disease. This review also describes the potential benefits of treating neurodegenerative diseases by modulating changes in microglial states. Therefore, inducing a shift from the neurotoxic to neuroprotective microglial state in neurodegenerative diseases induced by aging and chronic inflammation holds promise for the treatment of neurodegenerative diseases in the future.

Aim.This study was aimed at investigating the effects and molecular mechanisms of physical activity intervention on Parkinson’s disease (PD) and providing theoretical guidance for the prevention and treatment of PD.Methods.Four electronic databases up to December 2019 were searched (PubMed, Springer, Elsevier, and Wiley database), 176 articles were selected. Literature data were analyzed by the logic analysis method.Results.(1) Risk factors of PD include dairy products, pesticides, traumatic brain injury, and obesity. Protective factors include alcohol, tobacco, coffee, black tea, and physical activity. (2) Physical activity can reduce the risk and improve symptoms of PD and the beneficial forms of physical activity, including running, dancing, traditional Chinese martial arts, yoga, and weight training. (3) Different forms of physical activity alleviate the symptoms of PD through different mechanisms, including reducing the accumulation ofα-syn protein, inflammation, and oxidative stress, while enhancing BDNF activity, nerve regeneration, and mitochondrial function.Conclusion.Physical activity has a positive impact on the prevention and treatment of PD. Illustrating the molecular mechanism of physical activity-induced protective effect on PD is an urgent need for improving the efficacy of PD therapy regimens in the future.