Scimex: Adelaide and Chinese scientists have made a ground breaking molecular
discovery in their work to find a cure for Alzheimer's Disease. Prof
Xin-Fu Zhou, says the
discovery of one of the mechanisms of Alzheimer's Disease opens the door
to further research into potential treatments. "Currently, only a few drugs help with the symptoms of Alzheimer's Disease and there is no cure," he says. Alzheimer's
Disease accounts for nearly 70 per cent of all dementia cases. Dementia
affects a staggering 44 million people around the world, with more than
342,000 Australians living with dementia. Without a medical
breakthrough, the number of Australians with dementia is expected to be
almost 900,000 by 2050.
"Alzheimer's Disease is one of the most devastating diseases currently facing society," Prof Zhou says.
"Its
effects are devastating on the individual, their carer and family, and
the economic burden on health and aged care systems will only increase
without urgent further research."
Prof Zhou and Prof Wang's Molecular Psychiatry
article is titled p75 ectodomain is a physiological neuroprotective
molecule against amyloid-beta toxicity in the brain of Alzheimer's
Disease.
"Alzheimer's Disease is a kind of metabolic disease
which produces too much toxic metabolic product and causes breakdown of
nerve connectivity," Prof Zhou says.
"Neurodegenerative signals
such as amyloid-beta (Aβ) and the precursors of neurotrophins,
outbalance neurotrophic signals, causing synaptic dysfunction and
neurodegeneration.
"Fortunately, people normally have mechanisms
which produce sufficient amounts of nerve protective factors which can
prevent the damage of toxic metabolites to the brain.
"The
neurotrophin receptor p75 (p75NTR) is a receptor of Aβ and precursors of
neutrophins and mediates the toxicity of the neurodegenerative signals.
However, the shedding of its extracellular domain (P75ECD) of p75 from
the cell surface is a neuroprotective event and physiologically
regulated."
Profs Zhou and Wang discovered that in Alzheimer's
Disease, the full length p75 which causes nerve damage is increased but
the level of neuroprotective p75ECD in the brain and cerebral spinal
fluid is reduced to the abnormality in the process of p75ECD shedding.
They
showed that restoration of p75ECD to the normal level by brain delivery
of the gene encoding human p75ECD before or after Aβ deposition in the
brains of mice reversed the behavioural deficits and Alzheimer's
Disease-type pathologies, such as Aβ deposit, apoptotic (cell death)
events, neuroinflammation, Tau phosphorylation, and the loss of
dendritic spine, neuronal structures and synaptic proteins. They also
showed p75ECD can reduce amyloidogenesis by suppressing β-secretase
expression and activities.
"Our data demonstrates that p75ECD is a
physiologically neuroprotective molecule against Aβ toxicity and would
be a novel therapeutic target and biomarker for Alzheimer's Disease,"
Prof Zhou says.
"Further studies are required to validate p75ECD as a drug candidate and diagnostic marker in preclinical and clinical trials."