Heparin oligosaccharides as potential therapeutic agents in senile dementia.
Heparin is a glycosaminoglycan mixture currently used in prophylaxis and treatment of thrombosis. Heparin possesses non-anticoagulant properties, including modulation of various proteases, interactions with fibroblast growth factors, and anti-inflammatory actions. Senile dementia of Alzheimer's type is accompanied by inflammatory responses contributing to irreversible changes in neuronal viability and brain function. Vascular factors are also involved in the pathogenesis of senile dementia. Inflammation, endogenous proteoglycans, and assembly of senile plagues and neurofibrillary tangles contribute directly and indirectly to further neuronal damage. Neuron salvage can be achieved by anti-inflammation and the competitive inhibition of proteoglycans accumulation. The complexity of the pathology of senile dementia provides numerous potential targets for therapeutic interventions designed to modulate inflammation and proteoglycan assembly. Heparin and related oligosaccharides are known to exhibit anti-inflammatory effects as well as inhibitory effects on proteoglycan assembly and may prove useful as neuroprotective agents.
Ma
Qing
Q
Department of Pharmacology and Experimental Therapeutics, Stritch School ofMedicine, Loyola University Chicago, Maywood, IL 60153, USA. qingma@buffalo.edu
Cornelli
Umberto
U
Hanin
Israel
I
Jeske
Walter P
WP
Linhardt
Robert J
RJ
Walenga
Jeanine M
JM
Fareed
Jawed
J
Lee
John M
JM
D000544:Alzheimer Disease / Q000188:drug therapy*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D006493:Heparin / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008074:Lipoproteins / Q000502:physiology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009844:Oligosaccharides / Q000627:therapeutic use*; D012307:Risk Factors; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D008074:Lipoproteins; D018696:Neuroprotective Agents; D009844:Oligosaccharides; D015842:Serine Proteinase Inhibitors; C051928:lipoprotein-associated coagulation inhibitor; D016222:Fibroblast Growth Factor 2; D006493:Heparin