Current literature highlights - June 2001

• Book ID: 104438128
• Publisher: Elsevier Science
• Year: 2001
• Tongue: English
• Weight: 43 KB
• Volume: 3
• Category: Article
• ISSN: 1464-3383
• DOI: 10.1016/s1464-3383(04)80103-9

✦ Synopsis

Recently a number of groups have disclosed novel compounds derived from the peptidylprolyl isomerase (PPIase) inhibition domains of the immunosuppressive drugs FK506 and rapamycin. These non-immunosuppressive small molecules, with a molecular weigh of less than 500, were found to be potent neurotrophic agents in neurite outgrowth assays. Certain analogues, such as GPI 1046 (i) have also been shown to be effective in models of Parkinson's and Alzheimer's diseases. Dosing paradigms have shown these compounds to product both neuroprotective and neuroregenerative effects in models of CNS pathogenicity. The biological target for the exceptional neurotrophic activity of compounds such as (i) is not known, although FKBP-12 is a likely candidate since it is upregulated in models of CNS injury. It has been shown, however, there is no clear correlation between rotamase inhibition activity and ED 50 for neurite outgrowth.