Garcia_edit_EU Neurology 08/03/2010 16:16 Page 23
Pathology of the Cleaved Tau Protein
also co-purifies, like PHFs.
67
These abnormal associations may affect mechanisms involved in the genesis of AD are still unclear. Further
the stability of microtubules leading to disruption of the intracellular investigation of the truncation of tau as a contributor to AD may
transport and maintenance of synaptic contacts.
64,68,69
All of these data therefore generate new insights, leading to a better understanding of
support a pathological role for polymeric tau in the form of NFTs by this important neurological disorder. n
interfering with the normal functioning of the neurons. This, in
combination with the loss of the ability of tau to stabilise microtubules,
Gustavo Basurto-Islas is a PhD student, supervised by Professor García-Sierra, in
may also exert continuous toxicity during the progression of AD.
24,34,60,65
the Department of Cell Biology at the Centre of Research and Advanced Studies
of the National Polytechnical Institute in Mexico City. His research project in
In spite of the evidence suggesting NFTs are one of the major toxic
collaboration with Dr Jesús Avila has focused on the pathological role of tau
protein in Alzheimer’s disease.
candidates in AD, contradictory information has suggested that tau
species have no toxicity and aggregates are just an epiphenomenon
Siddhartha Mondragón-Rodríguez is a PhD student in the laboratory of Professor
resulting from the toxic properties of other pathological hallmarks of
García-Sierra at the Centre of Research and Advanced Studies of the National
Polytechnical Institute in Mexico City. His research project in collaboration with Drs
AD.
70,71
Some reports have demonstrated that neurodegeneration in
George Perry and Mark Smith is focused on the pathological processing of tau protein
transgenic models occurs without NFT formation,
72
and those neurons
in Alzheimer’s disease and related tauopathies.
bearing fibrillary lesions can survive for a long time.
73
These observations
Lester I Binder is the Abbott Labs/Burnham Professor of Genetic and Molecular
conversely suggested a more protective role for tau aggregates instead
Medicine and a Professor of Cell and Molecular Biology at Northwestern University
of a toxic effect produced for monomeric tau.
64
In transgenic mice,
Feinberg School of Medicine in Chicago. He has studied the normal function of tau
similar results were obtained, with memory impairment and neuronal
protein in the neuronal cytoskeleton.
loss occurring in the absence of tau aggregates.
74–76
Francisco Garcia-Sierra is a Professor of Cell Biology and Neuroscience at the
Department of Cell Biology in the Centre of Research and Advanced Studies of the
Conclusion
National Polytechnical Institute in Mexico City. He is a Member of the Society for
Neuroscience and has received several grants for his research from CONACyT-Mexico.
The implication of the toxicity of tau aggregates in neurodegeneration He was a post-doctoral fellow in Dr Binder’s laboratory at Northwestern University.
has been extensively discussed.
8,64,71,77–79
At present the precise
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