British Journal of Neuroscience Nursing, Год журнала: 2024, Номер 20(2), С. 54 - 59
Опубликована: Апрель 2, 2024
Physical activity is an essential part of managing and optimising health in all people, it even more necessary for those living with Parkinson's. This article explores the broad evidence base physical Parkinson's across disease symptom management, some barriers to engagement, role that healthcare professionals can play supporting this self-management optimisation.
Язык: Английский
Cell Death and Differentiation, Год журнала: 2023, Номер 30(6), С. 1416 - 1429
Опубликована: Апрель 12, 2023
Язык: Английский
Процитировано
37
Science Advances, Год журнала: 2023, Номер 9(28)
Опубликована: Июль 14, 2023
Intensive physical activity improves motor functions in patients with Parkinson's disease (PD) at early stages. However, the mechanisms underlying beneficial effects of exercise on PD-associated neuronal alterations have not been fully clarified yet. Here, we tested hypothesis that an intensive treadmill training program rescues striatal plasticity and cognitive deficits rats receiving intrastriatal injection alpha-synuclein (α-syn) preformed fibrils. Improved control visuospatial learning active animals were associated a recovery dendritic spine density lasting rescue physiological corticostriatal long-term potentiation (LTP). Pharmacological analyses LTP show modulations N-methyl-d-aspartate receptors bearing GluN2B subunits tropomyosin receptor kinase B, main brain-derived neurotrophic factor receptor, are involved these effects. We demonstrate has plastic induced by α-syn aggregates reduces spread toxic species to other vulnerable brain areas.
Язык: Английский
Процитировано
32
Frontiers in Neuroscience, Год журнала: 2025, Номер 18
Опубликована: Янв. 8, 2025
Parkinson's disease (PD) is characterized by progressive neurodegeneration within the nigrostriatum, leading to motor dysfunction. This systematic review aimed summarize effects of various exercise training regimens on protein or gene expression nigrostriatum and their role in neuroprotection function improvement animal models (PD). PubMed, EMBASE, Web Science were searched up June 2024 included sixteen studies that adhere PRISMA guidelines CAMARADES checklist scores ranging from 4 6 out 10. Various regimens, administered 5 days per week for 6.5 weeks, applied MPTP, 6-OHDA, PFF-α-synuclein-induced PD models. Exercise was found downregulate inflammatory pathway attenuating α-synuclein aggregation, inhibiting TLR/MyD88/IκBα signaling cascade NF-κB phosphorylation, decreasing pro-inflammatory cytokines IL-1β TNF-α while increasing anti-inflammatory IL-10 TGF-β nigrostriatum. It also inhibited ASC NLRP3 inflammasome complex reduced BAX/ Bcl-2 ratio caspase-1/3 proteins, thereby neuronal apoptosis elevated Pro-BDNF, BDNF, GDNF, TrkB, Erk1/2, providing neurotrophic support dopaminergic neurons. Furthermore, it upregulated TH, DAT, PSD-95, synaptophysin The findings suggested downregulated apoptotic pathways BDNF/GDNF These molecular changes contributed neuroprotection, neuron loss, improved CRD42024484537 https://www.crd.york.ac.uk/prospero/#recordDetails.
Язык: Английский
Процитировано
2
Journal of Neural Transmission, Год журнала: 2024, Номер 131(6), С. 663 - 674
Опубликована: Апрель 13, 2024
Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive degeneration of dopaminergic neurons in the substantia nigra and other brain regions. A key pathological feature PD abnormal accumulation α-synuclein protein within affected neurons, manifesting as Lewy bodies neurites. Despite extensive research efforts spanning several decades, underlying mechanisms disease-modifying therapies remain elusive. This review provides an overview current trends basic on PD. Initially, it discusses involvement mitochondrial dysfunction pathogenesis PD, followed insights into role lysosomal disruptions vesicular transport system. Additionally, delves physiological roles α-synuclein, crucial associated with pathophysiology. Overall, purpose this to comprehend state elucidating intricate outline future directions understanding disease.
Язык: Английский
Процитировано
9
International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(4), С. 3264 - 3264
Опубликована: Фев. 7, 2023
Parkinson’s disease (PD) is the most common α-synucleinopathy worldwide. The pathognomonic hallmark of PD misfolding and propagation α-synuclein (α-syn) protein, observed in post-mortem histopathology. It has been hypothesized that triggers oxidative stress, mitochondrial dysfunction, neuroinflammation, synaptic leading to neurodegeneration. To this date, there are no disease-modifying drugs generate neuroprotection against these neuropathological events especially α-synucleinopathy. Growing evidence suggests peroxisome proliferator-activated receptor (PPAR) agonists confer neuroprotective effects PD, however, whether they also an anti-α-synucleinopathy effect unknown. Here we analyze reported therapeutic PPARs, specifically gamma isoform (PPARγ), preclinical animal models clinical trials for suggest possible mechanisms acting downstream from receptors. Elucidating PPARs through mimic as closely will facilitate execution better PD.
Язык: Английский
Процитировано
17
Journal of Affective Disorders, Год журнала: 2023, Номер 341, С. 248 - 255
Опубликована: Авг. 25, 2023
The paper observes regulation of the expression levels NLRP3 and TLR4 in hippocampal CA1 neurons CUMS mice by aerobic exercise with constructing depression mouse model, order to explore neuroprotective mechanism on hippocampus depressed mice.24 healthy male 8-week-old C57BL/6 were randomly divided into CG, MG ME. Thirteen stress-stimulating factors formulated a program. underwent 28 days referenced clinical means for experimental research. study was approved Ethics Committee Yichun University (YCUEC IRB number LSK NO.2022.18). After model preparation, ME subjected moderate-intensity treadmill training 8 weeks. TST, FST SPT used detect depression-like behaviors each group. Nissl staining compare cell morphology region hippocampus. Immunohistochemical western blot changes NLRP3, other proteins hippocampus.The results neurobehavioral assessment showed that, immobility time TST significantly increased, index decreased mice. Compared MG, improved such as index. that mostly vacuolar-like, severe nuclear pyknosis. Abnormal morphological vacuolar-like pyknotic pyknosis reduced. Protein test TLR4, IL-1β IL-10 positive increased compared proportion cells significantly, while reduced, reduced.Systematic can effectively improve behavior through TLR4/NLRP3 inflammatory signaling pathway, provide an effective basis rehabilitation treatment depression.
Язык: Английский
Процитировано
13
Neurobiology of Disease, Год журнала: 2023, Номер 181, С. 106115 - 106115
Опубликована: Апрель 9, 2023
Parkinson's disease (PD) is a complex illness with constellation of environmental insults and genetic vulnerabilities being implicated. Strikingly, many studies only focus on the cardinal motor symptoms fail to appreciate major non-motor features which typically occur early in process are debilitating. Common comorbid psychiatric features, notably clinical depression, as well anxiety sleep disorders thought emerge before onset prominent deficits. In this review, we will delve into prodromal stage PD how neuropsychiatric pathology might unfold, followed by later disturbances. It also interest discuss animal models capture complexity illness, including depressive-like characteristics along impairment. remains be determined underlying processes contributes such comorbidity. But some toxicants microbial pathogens implicated instigate pro-inflammatory effects favoring α-synuclein accumulation damage brainstem neurons fueling evolution mood We posit that comprehensive animal-based research approaches needed time-dependent nature primary co-morbid symptoms. This allow for possibility intervention more novel targeted treatments fit not individual patient variability, but changes over time disease.
Язык: Английский
Процитировано
12
International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(9), С. 7830 - 7830
Опубликована: Апрель 25, 2023
Parkinson's disease with cognitive impairment (PD-CI) results in several clinical outcomes for which specific treatment is lacking. Although the pathogenesis of PD-CI has not yet been fully elucidated, it related to neuronal plasticity decline hippocampus region. The dopaminergic projections from substantia nigra are critical regulating hippocampal plasticity. Recently, aerobic exercise recognized as an effective therapeutic strategy enhancing through secretion various muscle factors. exact role FNDC5-an upregulated, newly identified myokine produced after exercise-in mediating and regional remains unclear. In this study, effect treadmill on synaptic was evaluated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced chronic PD models. showed that substantially alleviated motor dysfunction, cognition disorder, neuron degeneration induced by MPTP. Here, we discovered quadriceps, serum, brain FNDC5 levels were lower mice intervention restored levels. Moreover, enhanced pyramidal neurons via increased dopamine BDNF mice. direct protective achieved promoting binding integrin αVβ5 receptor, thereby improving Regarding indirect protection effect, promotes connection interaction between CD90 molecules membrane terminals. Our findings demonstrated could effectively alleviate disorders activation FNDC5-BDNF pathway enhance SNpc MPTP-induced model.
Язык: Английский
Процитировано
12
NeuroImmune Pharmacology and Therapeutics, Год журнала: 2024, Номер 3(1), С. 17 - 32
Опубликована: Март 1, 2024
Tay-Sachs disease (TSD) and its severe form Sandhoff (SD) are autosomal recessive lysosomal storage metabolic disorders, which often result into excessive GM2 ganglioside accumulation predominantly in lysosomes of nerve cells. Although patients with these diseases appear normal at birth, the progressive undegraded gangliosides neurons leads to early death accompanied by manifestation motor difficulties gradual loss behavioral skills. Unfortunately, there is still no effective treatment available for TSD/SD. The present study highlights importance cinnamic acid (CA), a naturally occurring aromatic fatty number plants, inhibiting process transgenic mouse model SD. Oral administration CA significantly attenuated glial activation inflammation reduced gangliosides/glycoconjugates cerebral cortex mice. Besides, oral also improved performance increased survival While assessing mechanism, we found that level peroxisome proliferator-activated receptor α (PPARα) brain mice remained unable reduce glycoconjugates, improve behavior increase lacking PPARα. Our results indicate beneficial function utilizes PPARα-dependent mechanism halt progression SD thereby longevity
Язык: Английский
Процитировано
5
Science Advances, Год журнала: 2025, Номер 11(7)
Опубликована: Фев. 12, 2025
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive accumulation of abnormal α-synuclein (α-syn) within dopaminergic neurons in substantia nigra region brain. Despite excessive α-syn being key to pathogenesis PD, mechanisms governing its clearance remain elusive. In this study, we found that endosomal sorting complex required for transport (ESCRT) system plays crucial role capturing and facilitating degradation ubiquitinated α-syn. The E3 ubiquitin ligase Listerin was promote K27-linked polyubiquitination α-syn, directing it endosome subsequent degradation. We showed deletion gene exacerbates progression mouse model whereas overexpression effectively mitigates PD mice. Consequently, our study reveals mechanism identifies as promising therapeutic target treatment PD.
Язык: Английский
Процитировано
0