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Common mechanisms in neurodegeneration

To the Editor:

Why, with all the progress in the field of neurodegeneration, do we still lack disease-modifying drugs that tackle the primary defect of severe cell loss? Part of the issue is that many cells are already dead before the symptoms appear, and we are probably attempting to treat the patients too late to make a difference. We still do not know whether the neurodegenerative disorders follow a unifying mechanism for disease initiation and propagation1. Accordingly, it is too soon to decide whether all these disorders should be treated in a similar fashion.

Neurodegeneration often results from the accumulation of misfolded aggregated proteins in different areas of the aging brain, and this process yields cell death and inflammatory damage in those brain areas. However, in some disorders, such as Huntington's disease, protein aggregates could have the opposite function, carrying out a protective role2. A recent study has challenged some of our ideas about Alzheimer's disease, concluding that tau aggregates seem to be a consequence rather than a cause of neurodegeneration3. Thus, it is unclear whether blocking this aggregation therapeutically would be beneficial or harmful.

The existence of common mechanisms for the pathogenesis of various neurodegenerative diseases could facilitate the development of new drugs to prevent these disorders. A probable common link among some of these disorders is the appearance of oxidative damage that results in neurodegeneration4. However, there is not enough work being done in the pharmaceutical industry to look for compounds that prevent oxidative stress or mitochondrial dysfunction.

More research should be done to determine whether there are common mechanisms for the different neurodegenerative disorders. This will aid in our understanding of disease mechanisms and will move drug development forward.


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  3. de Calignon, A. et al. Nature 464, 1201–1204 (2010).

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  4. Lin, M.T. & Beal, M.F. Nature 443, 787–795 (2006).

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Correspondence to Jesús Avila.

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Avila, J. Common mechanisms in neurodegeneration. Nat Med 16, 1372 (2010).

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