Drug Discovery Opinion

Amyloid peptide oligomers are believed to contribute to the pathology of Alzheimer’s Disease and much effort has gone into developing inhibitors of the β- and γ-secretases which are key to production of these peptides. An alternative approach to reducing amyloid peptide levels would be to increase their degradation. A number of proteases, including neprilysin, insulin-degrading enzyme and plasmin have been shown to degrade amyloid peptides.

A recent report now describes how increasing plasmin levels by inhibiting plasminogen activator inhibitor-1 (PAI-1) can lead to lowered brain amyloid levels. The PAI-1 inhibitor, PAZ-417, was found to lower brain and plasma amyloid levels and reverse cognitive deficits in mouse models of Alzheimer’s Disease.

PAZ-417 is currently undergoing Phase I clinical studies to investigate safety, tolerability and pharmacokinetics in young and elderly volunteers.

Bookmark It

Hide Sites

Related posts:

1. Glutaminyl Cyclase Implicated in Amyloid Plaque Formation Alzheimer’s disease is characterised by the presence of neurofibrillary tangles and deposits of amyloid peptides (Aβ) in the brain. N-terminally...
2. Calpain Inhibitors in Models of Alzheimer’s Disease Calpains are calcium-activated cysteine proteases which, when abnormally activated, can initiate degradation of proteins essential for neuronal survival. A report...
3. IL-6 Stimulates Amyloid Plaque Clearance Amyloid plaques, which deposit around nerve cells, and neurofibrillary tangles, which build up inside the cells, are the primary hallmarks...
4. Paradoxical Results for Alzheimer’s Drug Although not without opponents – and still unproven – the theory that reducing levels of β-amyloid peptides will lessen neuronal...
5. Targeting the Tangles Although the relative importance of β-amyloid plaques and tau protein tangles in the progression of Alzheimer’s disease has been the...

Related posts brought to you by Yet Another Related Posts Plugin.

 Email This Post

This entry was posted on Friday, August 29th, 2008 at 8:57 am and is filed under News. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.