ReviewNature reviews. Neuroscience2022
Motor and non-motor circuit disturbances in early Parkinson disease: which happens first?
Review in Nature reviews. Neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
117 citing papers in PubMed, 3 syntheses or guidelines pooled it, 227 citations in OpenAlex.
- Poor sleep quality among patients with Parkinson's disease: a meta-analysis and systematic review.Frontiers in psychiatry · 2025Pooled it
- Motor Memory Consolidation Deficits in Parkinson's Disease: A Systematic Review with Meta-Analysis.Journal of Parkinson's disease · 2023Pooled it
- Effects and parameters of community-based exercise on motor symptoms in Parkinson's disease: a meta-analysis.BMC neurology · 2022Pooled it
- Exploring Cognitive and Affective Outcomes Following Bilateral 6-Hydroxydopamine Lesions of the Substance Nigra or Striatum in Rats.Journal of neuroscience research · 2026Article
- Pesticide exposure and multidomain symptom burden in Parkinson's disease: a longitudinal triangulation study.NPJ Parkinson's disease · 2026Article
- Nigrostriatal dopaminergic vulnerability in Parkinson's disease: Neuroprotective strategies.Neural regeneration research · 2026Article
- Local brain network alterations in prodromal and De Novo Parkinson's disease: basal ganglia functional connectivity mediates the association between regional homogeneity and motor manifestations.Behavioral and brain functions : BBF · 2026Article
- Locus coeruleus α-synuclein overexpression induces prodromal Parkinsonian features in mice.NPJ Parkinson's disease · 2026Article
- Preservation of Extracellular and Tissue Dopamine During Tyrosine Hydroxylase Loss in Rat 6-OHDA Parkinson's Model: Selective Compensation Restricted to Substantia Nigra.International journal of molecular sciences · 2026Article
- Gut microbiota and SCFA biomarkers for early diagnosis of PD patients and differentiation of its motor subtypes.NPJ Parkinson's disease · 2026Article
- Pathogenic or Likely Pathogenic GRN Variants Are Found in 0.1% of Parkinson's Disease Patients.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Multi-dimensional diffusion MRI at ultra-high gradient strength for mapping axonal architecture and microstructure in the primate brain.bioRxiv : the preprint server for biology · 2026Article
- Gut-initiated alpha synuclein fibrils drive parkinsonism phenotypes: temporal mapping of REM sleep behavior disorder-like and other non-motor symptoms.Translational neurodegeneration · 2026Article
- Sex-Dependent Dynamics of Behavioural and Neuropathological Changes in an A53T Alpha-Synuclein Mouse Model of Parkinson's Disease.Cellular and molecular neurobiology · 2026Article
- Association between instrumental activities of daily living and incidence of Parkinson's disease: a nationwide population-based cohort study.NPJ Parkinson's disease · 2026Article
- Re-conceptualizing Parkinson's disease as a lifelong neurobiological trajectory: A framework for prevention.Neuroprotection (Chichester, England) · 2026Review
- Article
- Characterization of motor and non-motor features associated with bilateral nigral degeneration due to A53T alpha-synuclein in female rats.Scientific reports · 2026Article
- Parkinson's disease progression is shaped by longitudinal changes in cerebral compensation.Brain : a journal of neurology · 2026Article
- Cyclic Alternating Pattern and Sleep Microstructure in Parkinson's Disease: A Systematic Review and Meta-Analysis.Nature and science of sleep · 2026Review
57 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
For the last two decades, pathogenic concepts in Parkinson disease (PD) have revolved around the toxicity and spread of α-synuclein. Thus, α-synuclein would follow caudo-rostral propagation from the periphery to the central nervous system, first producing non-motor manifestations (such as constipation, sleep disorders and hyposmia), and subsequently impinging upon the mesencephalon to account for the cardinal motor features before reaching the neocortex as the disease evolves towards dementia. This model is the prevailing theory of the principal neurobiological mechanism of disease. Here, we scrutinize the temporal evolution of motor and non-motor manifestations in PD and suggest that, even though the postulated bottom-up mechanisms are likely to be involved, early involvement of the nigrostriatal system is a key and prominent pathophysiological mechanism. Upcoming studies of detailed clinical manifestations with newer neuroimaging techniques will allow us to more closely define, in vivo, the role of α-synuclein aggregates with respect to neuronal loss during the onset and progression of PD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.