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Nerve growth factor: structure, function and therapeutic implications for Alzheimer's disease.

Publication ,  Journal Article
Lad, SP; Neet, KE; Mufson, EJ
Published in: Curr Drug Targets CNS Neurol Disord
October 2003

Over the past decade, neurotrophic factors have generated much excitement for their potential as therapy for neurological disorders. In this regard, nerve growth factor (NGF), the founding member of the neurotrophin family, has generated great interest as a potential target for the treatment of Alzheimer's disease (AD). This interest is based on the observation that cholinergic basal forebrain (CBF) neurons which provide the major source of cholinergic innervation to the cerebral cortex and hippocampus undergo selective and severe degeneration in advanced AD and that these neurons are dependent upon NGF and its receptors for their survival. In fact, NGF transduces its effects by binding two classes of cell surface receptors, TrkA and p75(NTR), both of which are produced by CBF neurons. This review focuses on NGF/receptor binding, signal transduction, regulation of specific cellular endpoints, and the potential use of NGF in AD. Alterations in NGF ligand and receptor expression at different stages of AD are summarized. Recent results suggest that cognitive deficits in early AD and mild cognitive impairment (MCI) are not associated with a cholinergic deficit. Thus, the earliest cognitive deficits in AD may involve brain changes other than simply cholinergic system dysfunction. Recent findings indicate an early defect in NGF receptor expression in CBF neurons; therefore treatments aimed at facilitating NGF actions may prove highly beneficial in counteracting the cholinergic dysfunction found in end-stage AD and attenuating the rate of degeneration of these cholinergic neurons.

Duke Scholars

Published In

Curr Drug Targets CNS Neurol Disord

DOI

ISSN

1568-007X

Publication Date

October 2003

Volume

2

Issue

5

Start / End Page

315 / 334

Location

Netherlands

Related Subject Headings

  • Structure-Activity Relationship
  • Signal Transduction
  • Receptor, Nerve Growth Factor
  • Neurology & Neurosurgery
  • Nerve Growth Factor
  • Humans
  • Drug Delivery Systems
  • Animals
  • Alzheimer Disease
  • 3214 Pharmacology and pharmaceutical sciences
 

Citation

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Lad, S. P., Neet, K. E., & Mufson, E. J. (2003). Nerve growth factor: structure, function and therapeutic implications for Alzheimer's disease. Curr Drug Targets CNS Neurol Disord, 2(5), 315–334. https://doi.org/10.2174/1568007033482724
Lad, Shivanand P., Kenneth E. Neet, and Elliott J. Mufson. “Nerve growth factor: structure, function and therapeutic implications for Alzheimer's disease.Curr Drug Targets CNS Neurol Disord 2, no. 5 (October 2003): 315–34. https://doi.org/10.2174/1568007033482724.
Lad SP, Neet KE, Mufson EJ. Nerve growth factor: structure, function and therapeutic implications for Alzheimer's disease. Curr Drug Targets CNS Neurol Disord. 2003 Oct;2(5):315–34.
Lad, Shivanand P., et al. “Nerve growth factor: structure, function and therapeutic implications for Alzheimer's disease.Curr Drug Targets CNS Neurol Disord, vol. 2, no. 5, Oct. 2003, pp. 315–34. Pubmed, doi:10.2174/1568007033482724.
Lad SP, Neet KE, Mufson EJ. Nerve growth factor: structure, function and therapeutic implications for Alzheimer's disease. Curr Drug Targets CNS Neurol Disord. 2003 Oct;2(5):315–334.

Published In

Curr Drug Targets CNS Neurol Disord

DOI

ISSN

1568-007X

Publication Date

October 2003

Volume

2

Issue

5

Start / End Page

315 / 334

Location

Netherlands

Related Subject Headings

  • Structure-Activity Relationship
  • Signal Transduction
  • Receptor, Nerve Growth Factor
  • Neurology & Neurosurgery
  • Nerve Growth Factor
  • Humans
  • Drug Delivery Systems
  • Animals
  • Alzheimer Disease
  • 3214 Pharmacology and pharmaceutical sciences