InFo Neurologie + Psychiatrie, Journal Year: 2024, Volume and Issue: 26(11), P. 34 - 43
Published: Nov. 1, 2024
Parkinsonism & Related Disorders, Journal Year: 2024, Volume and Issue: 122, P. 106077 - 106077
Published: March 3, 2024
These facts argue against the gain-of-function synucleinopathy hypothesis, which proposes that Lewy pathology causes Parkinson's disease: (1) most brains from people without neurological symptoms have multiple pathologies; (2) neither type nor distribution correlate with disease severity or progression in disease; (3) aggregated α-synuclein form of bodies is not a space-occupying lesion but insoluble fraction its precursor, soluble monomeric α-synuclein; (4) spread passive, occurring by irreversible nucleation, active replication; and (5) low cerebrospinal fluid levels predict brain atrophy clinical progression. The transformation into may occur as response to biological, toxic, infectious stressors whose persistence perpetuates nucleation process, depleting normal eventually leading neuronal death. We propose testing loss-of-function synucleinopenia hypothesis evaluating neurodegenerative rescue effect replenishing α-synuclein.
Language: Английский
Citations
17
Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 12
Published: Jan. 22, 2025
Parkinson’s disease is a progressive neurodegenerative that destroys substantia nigra dopaminergic neurons, causing tremors, bradykinesia, rigidity, and postural instability. Current treatment approaches primarily focus on symptom management, employing pharmacological, non-pharmacological, surgical methods. However, these treatments often result in fluctuating symptoms, side effects, progression. Here, the authors have reviewed emerging field of nanomedicine as promising path for treatment, emphasizing its potential to overcome limitations traditional therapies. Nanomedicine utilizes nanoparticles targeted drug delivery, leveraging their small size high surface area volume ratio cross blood-brain barrier deliver therapeutic agents directly affected brain regions. Various nanoparticles, including lipid-based, polymeric, metallic, carbon-based, shown treatment. Additionally, nanocarrier systems like liposomes, nanogels, dendrimers, solid lipid offer controlled sustained release agents, enhancing bioavailability reducing effects. This review provides insights into pathophysiology disease, highlighting mechanisms neurodegeneration, role alpha-synuclein, disruption pathways. It further discusses application gene therapy conjunction with interventions.
Language: Английский
Citations
2
Nature Reviews Neurology, Journal Year: 2024, Volume and Issue: 20(12), P. 695 - 707
Published: Nov. 4, 2024
Language: Английский
Citations
10
Neuron, Journal Year: 2024, Volume and Issue: unknown
Published: June 1, 2024
Language: Английский
Citations
8
npj Parkinson s Disease, Journal Year: 2024, Volume and Issue: 10(1)
Published: March 2, 2024
Language: Английский
Citations
7
Translational Psychiatry, Journal Year: 2024, Volume and Issue: 14(1)
Published: Sept. 23, 2024
Language: Английский
Citations
4
npj Parkinson s Disease, Journal Year: 2025, Volume and Issue: 11(1)
Published: March 4, 2025
Based on the prevailing α-synuclein "gain-of-function" hypothesis, reducing levels and removing its aggregates is a current focus of disease-modifying therapies for Parkinson's disease. Emerging evidence "loss-of-function" suggests that it may be necessary to replenish monomeric levels. We propose personalized comprehensive approach different subgroups based whether likely contribute disease pathogenesis through "gain-of-function", "loss-of-function", or both mechanisms.
Language: Английский
Citations
0
Clinics and Practice, Journal Year: 2025, Volume and Issue: 15(3), P. 65 - 65
Published: March 17, 2025
Alpha-synuclein has been associated with neurodegeneration, especially in Parkinson’s disease (PD). This study aimed to review clinical, biochemical, and neuroimaging markers management of prodromal synucleinopathies. The state synucleinopathies can be better understood PD pathophysiology, it separated into premotor pre-diagnostic phases. incidence patients phase symptoms ranges from 0.07 14.30, the most frequently studied pathology is REM behavioral disorder (RBD). Neuroimaging are related dopamine denervation, brain perfusion changes, gross anatomy peripheral abnormalities. α-synuclein assays (SAA) CSF revealed high sensitivity (up 97%) specificity 92%); last decade, there was development other matrices (blood, skin, olfactory mucosa) for obtaining quantitative qualitative α-synuclein. Other biomarkers neurofilament light chain, DOPA decarboxylase, multiplexed mass spectrometry assay. Regarding genetic counseling α-synucleinopathies, an important topic clinical practice discuss high-risk individuals should involve basic principles autonomy, beneficence, non-maleficence. Some themes that reviewed involvement physical activity, diet (including alcohol, coffee, vitamin supplementation), smoking, sleep, stress pathophysiology number trials still scarce, studies evaluating intervention even lower.
Language: Английский
Citations
0
Neuromethods, Journal Year: 2024, Volume and Issue: unknown, P. 277 - 294
Published: Sept. 18, 2024
Language: Английский
Citations
0
InFo Neurologie + Psychiatrie, Journal Year: 2024, Volume and Issue: 26(11), P. 34 - 43
Published: Nov. 1, 2024
Citations
0