Low molecular weight glycosaminoglycan blockade of beta-amyloid induced neuropathology.
Previous studies have shown different roles for proteoglycans and glycosaminoglycans (GAGs) in Alzheimer's disease (AD) neuropathology. Using a rat model of beta-amyloid induced neuropathology, we tested whether low molecular weight glycosaminoglycans (Certoparin and C6) could be useful as preventative agents and/or as a potential therapeutic treatment for AD. Chronic subcutaneous low molecular weight glycosaminoglycan injections beginning either before or after an intra-amygdaloid beta-amyloid-(25-35) injection blocked abnormal intracellular tau changes and reactive astrocytosis but did not affect beta-amyloid's aggregation state. Also, low molecular weight glycosaminoglycan injections beginning 1 day prior to sacrifice did not block the effects of beta-amyloid nor did injections of a disaccharide, suggesting chronic low molecular weight glycosaminoglycan treatment is needed to block the effects of beta-amyloid. Furthermore, these data indicate that there is a molecular weight range of active low molecular weight glycosaminoglycans in this model; and supports the investigation of low molecular weight glycosaminoglycans as a preventative and/or therapeutic treatment of beta-amyloid induced neuropathology.
Walzer
Mark
M
Department of Pharmacology, Loyola University Chicago Medical Center, 2160 South First Avenue, Rm. 2638, Maywood, IL 60153, USA.
Lorens
Stanley
S
Hejna
Matthew
M
Fareed
Jawed
J
Hanin
Israel
I
Cornelli
Umberto
U
Lee
John M
JM
D016229:Amyloid beta-Peptides / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D006025:Glycosaminoglycans / Q000494:pharmacology; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D008297:Male; D010446:Peptide Fragments / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D016875:tau Proteins / Q000032:analysis / Q000378:metabolism
D016229:Amyloid beta-Peptides; D006025:Glycosaminoglycans; D006495:Heparin, Low-Molecular-Weight; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D016875:tau Proteins; C403769:certoparin