Regulation of a-Synuclein Membrane Binding and Its Implications
Bibliographic record
Abstract
Introduction 1.1 Parkinson's disease and Lewy bodiesParkinson's disease (PD) is the most prevalent neurodegenerative disease that affects motor control, although dementia, depression, and other psychiatric symptoms are occasionally present (reviewed in Jankovic, 2008).The motor symptoms include resting tremors, bradykinesia/akinesia, rigidity, and postural instability, and are associated with the death of dopaminergic neurons in the substantia nigra pars compacta (SNpc) (Lloyd and Hornykiewicz, 1970; reviewed in Saper, 1999) and noradrenergic neurons in the locus coeruleus (Mann and Yates, 1983; Gaspar et al., 1991).Degeneration of these neurons disrupts basal ganglia circuitry of the brain and interferes with the initiation of voluntary movement (Levy et al., 1997).Another pathological characteristic of the disease is the presence of the intracellular protein aggregates known as Lewy bodies and Lewy neurites (Hughes et al., 1992), described initially by Frederick Lewy in 1912, that were associated with dying dopaminergic neurons in the SNpc by Tretiakoff (reviewed in Holdorff, 2006).Lewy bodies are also present in other brain regions outside the SNpc, and may appeat first in the glossopharyngeal, vagal, and olfactory centres (Braak et al., 2003).The disruption of these regions is now linked to a preclinical phase of PD that includes perturbations of smell, gastrointestinal motility, and sleep patterns prior to the development of motor impairments coincident with neurodegeneration and inclusions in the midbrain.These intraneuronal aggregates are composed of lipids and various proteins including -synuclein, ubiquitin, and neurofilaments (Spillantini et al., 1998; reviewed in Cookson, 2005).Whether Lewy bodies directly cause cytotoxicity or are formed as compensatory activation of survival pathways remains under debate.Nevertheless, the presence of Lewy bodies is an essential component of post-mortem diagnoses of PD (Christine and Aminoff, 2004; reviewed in Jankovic, 2008). α-Synuclein in Parkinson's disease-Synuclein is important to understanding the etiology of PD both because it is the main pathological component of Lewy bodies and because mutations and changes in its expression are linked to familial PD.Three missense mutations causing single amino acid www.intechopen.com How to referenceIn order to correctly reference this scholarly work, feel free to copy and paste the following: Robert H.C. Chen, Sabine Wislet-
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".