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Molecular pathways to neurodegeneration

Nature Medicine volume 10, pages S2–S9 (2004)Cite this article

Abstract

The molecular bases underlying the pathogenesis of neurodegenerative diseases are gradually being disclosed. One problem that investigators face is distinguishing primary from secondary events. Rare, inherited mutations causing familial forms of these disorders have provided important insights into the molecular networks implicated in disease pathogenesis. Increasing evidence indicates that accumulation of aberrant or misfolded proteins, protofibril formation, ubiquitin-proteasome system dysfunction, excitotoxic insult, oxidative and nitrosative stress, mitochondrial injury, synaptic failure, altered metal homeostasis and failure of axonal and dendritic transport represent unifying events in many slowly progressive neurodegenerative disorders.

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Figure 1: Histology and structures related to AD.
Figure 2: Histology and structures related to PD.
Figure 3: DJ-1 and PINK1 proteins in PD.
Figure 4: Aggregation and domain structure of Htt in HD.

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Acknowledgements

We thank Eliezer Masliah and Mark Barsoum for providing histological images, Huaxi Xu for reading the manuscript and our colleagues for helpful discussions. This work was supported by NIH grants R01 NS44314 and R01 NS047456 (to E.B-W.) and P01 HD29587, R01 EY05477, R01 EY09024, R01 NS43242, R01 NS44326 and R01 NS41207 (to S.A.L.).

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  1. Center for Neuroscience & Aging, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, 92037, California

    Ella Bossy-Wetzel & Stuart A Lipton

  2. Program in Bioinformatics & Systems Biology, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, 92037, California

    Robert Schwarzenbacher

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  1. Ella Bossy-Wetzel
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Correspondence to Ella Bossy-Wetzel or Stuart A Lipton.

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S.A.L. is the named inventor on patents for the drug memantine to treat neurodegenerative disorders. Under agreements between Children's Hospital/Harvard Medical School and Forest Laboratories/Merz & Co./Neurobiological Technologies, Inc., S.A.L. is thus entitled to a share of sales royalties received by the hospital. S.A.L. owns no stock in these companies. The terms of this arrangement are being managed by Harvard Medical School in accordance with its conflict-of-interest policies.

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Bossy-Wetzel, E., Schwarzenbacher, R. & Lipton, S. Molecular pathways to neurodegeneration. Nat Med 10 (Suppl 7), S2–S9 (2004). https://doi.org/10.1038/nm1067

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