Nerve Growth Factor, Aging and Alzheimer's disease
Bibliographic record
Abstract
Since the cholinergic hypothesis of geriatric memory dysfunction was proposed by Bartus and colleagues in 1982, studies conducted in animals and humans so far have failed to obtain evidence for the involvement of NGF in normal Aging and/or in the pathophysiology of Alzheimer's disease (AD). It has been hypothesized that age-related degeneration of basal forebrain cholinergic neurons (BFCN) may be caused by the altered endogenous NGF maturation either by reduced responsiveness to NGF, by reduced NGF transport or by the failure in coupling to second messengers. NGF administered in the CNS of AD patients led to undesirable side effects, most likely mediated by p75 neurotropin receptor (p75NTR) rather than through its specific TrkA receptor. Thus, we decided to treat behaviorally characterize age-impaired (AI) rats with small proteolytic- resistant peptide mimetic of the TrkA receptor, named D3. This selective partial agonist of the TrkA receptor reversed the atrophy of the BFCN, ameliorating the cognitive decline observed in AI rats. The realization that the precursor of NGF (proNGF) might play a biological role in the CNS, raised questions regarding the regulatory mechanisms leading to its release, as well as the control of the proNGF to NGF ratio and, ultimately, the degradation of the NGF molecule. To answer these questions, we performed in vitro and in vivo studies aimed at elucidating the preferential NGF form released from the cerebral cortex, and the biochemical pathway leading to NGF maturation and degradation. These studies have revealed that proNGF is the main releasable form of the neurotrophin and that the maturation and degradation of NGF largely occurs in the extracellular space with the involvement of a complex protease cascade. The newly described mechanism for NGF conversion and degradation was found compromised in Alzheimer's disease. In brief, we found a failure in the conversion of proNGF to NGF, which was exacerbated by an increased NGF degrad
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".