Title: Development and Uses of Small Molecule Ligands of TrkA Receptors
Abstract: Nerve Growth Factor (NGF), is a polypeptide that elicits widespread biological effects via interaction with a tyrosine kinase receptor termed TrkA (Kaplan et al., 1991). NGF a member of the neurotrophin (NT) family of growth factors is responsible for the survival, differentiation and maintenance of specific sensory, sympathetic and cholinergic neuronal populations (Levi-Montalcini, 1987). The NGF dependent cholinergic basal forebrain and septum neurons are areas implicated in memory and learning which are severely affected by neuronal loss in Alzheimer's disease (Hefti and Will, 1987). The neurotrophic hypothesis states that innervated tissues produce NTs which coordinate neuronal growth and programmed death during development (Purves et al., 1985). In adulthood NT levels stabilize at low levels thought to be sufficient to maintain the neuronal phenotype. While NT levels increase upon neuronal injury they do not attain levels found in development. It appears that the inability to rescue neurons from trauma or disease induced cell death may be due to inadequate NT production, because neuronal popUlations can be rescued by NGF treatment (Cuello et al., 1993) (Table 1). Agonistic small molecule TrkA ligands with improved pharmacological properties may be useful for the treatment of stroke or neurodegenerative diseases, or for treatment of neoplastic diseases (neuroblastoma, medulloblastoma, melanoma) that respond to neurotrophins. Herein, we describe the development and uses of artificialligands of TrkA. These small molecule ligands are either structural mimics of NGF or structural mimics of anti-TrkA monoclonal antibodies (Figure 1).
Publication Year: 1998
Publication Date: 1998-01-01
Language: en
Type: book-chapter
Indexed In: ['crossref']
Access and Citation
Cited By Count: 1
AI Researcher Chatbot
Get quick answers to your questions about the article from our AI researcher chatbot