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Non-Anticoagulant Actions of Glycosaminoglycans (GAGs)

The Therapeutical Approach to Alzheimer’s Disease

  • Chapter
Nonanticoagulant Actions of Glycosaminoglycans

Summary

Glycosaminoglycans (GAGs) relationship with brain structures is analyzed in view of their role in the pathophysiology of Alzheimer’s disease (AD or SDAT; senile dementia Alzheimer’s type). The difference between Proteoglycans (PGs) and GAGs is considered the key for the interpretation of the two opposite roles played by these molecules. PGs are one of the possible determinants of AD whereas GAGs are tied to tentative therapeutical approaches in AD. These opposite positions are considered referring to both the main microstructures of the brain (e.g. cell surface, basement membrane, Extracellular Matrix) and the functional macrostructures (e.g. blood-brain barrier; BBB). A particular emphasis was given to the main AD markers:[amyloid substance, neurofibrillary tangles (NFT) and cerebral vessel microangiopathy] in order to show the background of AD therapy with GAP(glycosaminoglycan polisulfate). The modification of the basement membrane of the BBB, the reaction of the Extracellular Matrix (ECM) and the consequent neuronal damage could derive from the presence of antibodies against the protein core of a HSPG (heparan sulfate proteoglycan). The positive data obtained in Phase II, III and IV clinical trials with GAP administration suggest that GAGs may represent more than an orphan theory in the management of AD.*

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Abbreviations

Aβ:

amyloid beta protein

AchE:

acetylcholinesterase

ACT:

α 1-antichimotripsin

AD:

Alzheimer’s disease

AGP:

manual for the documentation of psychopathology in gerontopsychiatry

Apo E:

apolipoprotein E (E2, E3, E4)

Apo J:

apolipoprotein J

ATIII:

antithrombin III

BBB:

blood-brain barrier

βAPP:

beta amyloid protein precursor

BchE:

butyirylcholinesterase

BLIPS:

biomedical laboratory information process system

CBF:

cerebral blood flow

CGI:

clinical global impression

CS:

chondroitin sulfate

Ch4S:

choindroitin 4 sulfate

Ch6S:

chondroitin 6 sulfate

CFS:

cerebro spinal fluid

CMRO2 :

cerebral metabolism regional oxygen

CMRglu:

cerebral metabolism regional glucose

CNS:

central nervous system

CSPG:

chondroitin sulfate proteoglycan

DSM-III:

diagnostic and statistical manual of mental disorders

DOPAC:

3,4-dihydroxyphenyl acetic acid

DS:

dermatan sulfate

DSPG:

dermatan sulfate proteoglycan

EHS:

Hengelbreth-Holm-Swarm mouse sarcoma

FAD:

Alzheimer’s disease familiar type

FGF:

fibroblast growth factor

GAGs:

glycosamynoglicans

GAP:

glycosaminoglycan polisulfate

GDN/PN-1:

glial derived nexin/protein nexin-1

GDS:

global deterioration scale

GPI:

Glycosylphosphatidiyl-inisitol

ECDEU:

early clinical drug evaluation

ECM:

extracellular matrix

HA:

hyaluronic acid

HAPG:

hyaluronic acid proteoglycan

HC II:

heparin cofactor II

HDL:

high density lipoprotein

HEP:

heparin

HEPG:

heparin proteoglycan

5-HIAA:

5-hydroxyindolacetic acid

HIS:

Hachinski ischemic score

HS:

heparan sulfate

HSPG:

heparan sulfate proteoglycan

HVA:

homovanillic acid

KS:

keratan sulfate

LDL:

low density lipoprotein

LRP:

low density lipoprotein receptor protein

LRU:

lipasemic releasing unit

MAO-B:

monoamine oxidase type B

MID:

multi infarct dementia

MHPG:

3-3-methoxy-4-hydroxy-phenylglycol

MMSE:

mini mental state examination

MRI:

magnetic resonance imaging

MT:

microtubules network

NFT:

neurofibrillary tangles

NGF:

nerve growth factor

NSAIDs:

non steroidal antiinflammaroty drugs

PAI:

plasminogen activator inhibitor

PD:

primary dementia

PET:

positron emission tomography

PG:

proteoglycan

PHF:

paired helical filaments

PSPMSQ:

Pfeiffer short portable mental status questionnaire

PrP-res:

prion protein protease resistant

PS:

protamine sulfate

rCBF:

regional cerebral blood flow

sc+-MNBn:

scrapie infected cell line

SCAG:

Sandoz clinical assessment geriatric

SDAT:

senile dementia of the Alzheimer type

SHGRS:

Stuard hospital geriatric scale

SP:

seniles plaques

SPECT:

single photon emission computed tomography

TGF-β:

transforming growth factor beta

t.i.d.:

three times per day (ter in die)

tPA:

tissue plasminogen activator

uPA:

urokinase plasminogen activator

VLDL:

very low density lypoprotein

WAIS:

Weschler adult intelligence scale

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  1. Department of Pharmacology and Experimental Therapeutics, Loyola University Stritch School of Medicine, 2160 South First Avenue, Maywood, Illinois, 60153, USA

    Umberto Cornelli

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  1. University of Heidelberg, Mannheim, Germany

    Job Harenberg

  2. G. Ronzoni Institute, Milan, Italy

    Benito Casu

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© 1996 Plenum Press, New York

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Cornelli, U. (1996). Non-Anticoagulant Actions of Glycosaminoglycans (GAGs). In: Harenberg, J., Casu, B. (eds) Nonanticoagulant Actions of Glycosaminoglycans. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0371-8_20

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