Journal of Molecular Neuroscience

, Volume 24, Issue 1, pp 149–153

Transforming growth factor-β signaling pathway as a therapeutic target in neurodegeneration


DOI: 10.1385/JMN:24:1:149

Cite this article as:
Wyss-Coray, T. J Mol Neurosci (2004) 24: 149. doi:10.1385/JMN:24:1:149


Neurodegenerative diseases are becoming an increasing social and economical burden as our population ages; but current knowledge of the processes leading to these diseases is still limited, and no effective treatments are available. Neurodegeneration in Alzheimer’s disease (AD) is the most common cause of dementia and afflicts an estimated 4 million people in this country alone. Because accumulation of β-amyloid (Aβ) peptide appears central to AD pathogenesis, large efforts have been directed at understanding and interfering with Aβ production or aggregation. These efforts have largely identified the processes resulting in Aβ production from the larger amyloid precursor protein (APP) and have revealed that Aβ peptide is also produced at low levels in the healthy brain. Interestingly, Aβ production is rapidly increased after neuronal injury, and traumatic brain injury is a known risk factor for AD and Parkinson’s disease. In contrast, brain injury in young individuals does not seem to result in AD, and brain injury in animal models can promote Aβ clearance. This suggests that certain factors associated with injury might be able to reduce the accumulation of Aβ. Accumulation of Aβ peptide might be reduced either directly by stimulating phagocytes or other Aβ-degrading processes, or indirectly, by reducing neuronal injury and thus lowering the production of Aβ peptide. Directing the brain’s natural mechanisms for clearing Aβ or increasing neuroprotection might therefore be reasonable approaches in interfering with AD pathogenesis.

Index Entries

Cytokine neurodegeneration amyloid TGF-β signaling 

Copyright information

© Humana Press Inc 2004

Authors and Affiliations

  1. 1.Department of Neurology and Neurological SciencesStanford University School of MedicineStanford
  2. 2.GRECC, VA Palo Alto Health Care SystemPalo Alto

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