Of prions, Alzheimer's and Parkinson's Latest news on protein-folding
diseases
by Danielle Buch, BSc, BA
Online Facts and Stats
incorrect folding of proteins is thought
to be the cause of neurodegenerative disorders like Alzheimer's
(AD), with ß-amyloid, and Parkinson's, with alpha-synuclein
transmissible spongiform encephalopathies
(TSE) - i.e. prion diseases, including new variant Creutzfeldt-Jakob
disease (vCJD) - are also a form of amyloidosis
all healthy nerve cells have a normal prion
which folds properly and remains soluble (PrPC);
infectious prion (PrPSc) triggers
the others to misfold
another type of protein misfolding occurs
in p53, a tumour-suppressing protein; it's thought to occur in
95% of lung cancers and 50% of cancers, generally
prion infection of nerve cells increases
the free cholesterol in their membranes and abnormally activates
an enzyme implicated in the depletion of neurons. This effect
can't be replicated by stimulating synthesis or adding exogenous
cholesterol
prions seem to directly affect cholesterol
regulation
Alzheimer's is linked to diabetes - insulin
receptors are present at nerve synapses; when these are blocked
by amyloid ß-derived diffusible ligands, memory functions
fail; AD brains are insulin-resistant; AD is sometimes referred
to as diabetes type 3
proteins from AD patients seed themselves
like infectious prions - i.e. when injected into mice, they trigger
ß-amyloid lesions
prions in vCJD also accumulate in lymphoid
organs
Canadians have invented a test for vCJD
to one day be able to screen human donated blood
in some experiments, mice fed TSE-infected
material all died, but no high titres of prions were found - leading
researchers to wonder whether an independent infectious agent
may be the culprit - a virus theory has been suggested
Sites worth a look If neurodegenerative diseases can result from disturbances
in membrane cholesterol, what are the repercussions - both on cholesterol
management and treatment of illness? www.bio
medcentral.com/content/ pdf/1741-7007- 6-8.pdf
A new Centre for Prions and Protein Folding
Diseases has opened at the University of Alberta. While the focus
is on infectious prions, they'll look at other protein-folding diseases
as well: www.express
news.ualberta.ca/ article.cfm?id=8924
A symposium held in Italy on Protein Folding
and Disease has background articles of interest as well as links
to challenges for developing effective treatment strategies: www.nature.com/horizon/
proteinfolding/index.html
New practice guidelines on dementia were issued
in Dec. 2007. Essentially, they address the use of 3 cholinesterase
inhibitors as well as memantine for Alzheimer's and other dementias,
emphasize nonpharmacologic interventions to target emotional well-being,
and point out the advantages of pharmacologic treatment of depression.
They no longer recommend vitamin E as a treatment for AD, as health
risks have been associated with high doses. They suggest limiting
the use of antipsychotic drugs - both typical and atypical - as
they confer an increased mortality risk on people with dementia.
If not effective, they should be discontinued: www.psychiatryonline.com/
content.aspx? aID=152171.
