Drug development and PET-diagnostics for Alzheimer's disease.
The exact cause of Alzheimer's disease is still unknown; despite the dramatic progress in understanding. Most gene mutations associated with Alzheimer's disease point to the amyloid precursor protein and amyloid beta. The alpha-, beta- and gamma-secretases are the three executioners of amyloid precursor protein processing. Significant progress has been made in the selective inhibition of these proteases, regardless of the availability of structural information. Several peptidic and non-peptidic leads were identified and first drug candidates are in clinical trials. Cholesterol lowering drugs and metal chelators are also in advanced clinical stages as disease modifiers. Successful trials demand either large cohorts or reliable markers for Alzheimer's disease. Therefore, several radiomarkers are under investigation to support such clinical trials.
Schmidt
Boris
B
Clemens Schöpf-Institute for Organic Chemistry and Biochemistry, TU Darmstadt, Petersenstr. 22, D-64287 Darmstadt, Germany. schmibo@oc.chemie.tu-darmstadt.de
Braun
Hannes A
HA
Narlawar
Rajeshwar
R
D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010450:Endopeptidases; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D018696:Neuroprotective Agents / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals
D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; C414614:OM99-2; D009842:Oligopeptides; D019275:Radiopharmaceuticals; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human