Recent advances in the genetics of amyotrophic lateral sclerosis and frontotemporal dementia: common pathways in neurodegenerative disease
1 Department of Physiology, Anatomy and Genetics , 2 Department of Clinical Neurology, University of Oxford and 3 Department of Neuropathology, University of Oxford, Henry Wellcome Building of Gene Function, South Parks Road, Oxford OX1 3QX, UK
* To whom correspondence should be addressed. Tel: +44 1865285875; Fax: +44 1865790493; Email: kevin.talbot{at}clneuro.ox.ac.uk
Received July 19, 2006; Accepted July 27, 2006
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease classically defined by the impairment of the voluntary motor system and ubiquitin-positive intraneuronal aggregates in anterior horn cells. Frontotemporal dementia (FTD) is a common form of neurodegenerative dementia and presents with personality change associated in a significant subgroup of patients with cortical ubiquitin-only neuropathology (FTD-U). Careful study of ALS as well as FTD patient cohorts suggests clinical as well as pathological overlap of ALS with FTD. The idea that this reflects a shared pathogenesis has received strong support from the identification of new genetic loci on chromosome 9p and of mutations in specific genes (CHMP2B and DCN1) in families with co-segregation of ALS and FTD. The identification of two further genetic causes of FTD-U with (rare) ALS (PGRN) or without ALS (VCP) also provides a starting point for exploring the pathways associated with ubiquitin-mediated protein mishandling in FTD-U and ALS. Pure ALS, through ALS with cognitive impairment and ALS–FTD to pure FTD-U, may represent a continuous spectrum of ubiquitin-associated neurodegenerative disease.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. M. Igaz, L. K. Kwong, Y. Xu, A. C. Truax, K. Uryu, M. Neumann, C. M. Clark, L. B. Elman, B. L. Miller, M. Grossman, et al. Enrichment of C-Terminal Fragments in TAR DNA-Binding Protein-43 Cytoplasmic Inclusions in Brain but not in Spinal Cord of Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis Am. J. Pathol., July 1, 2008; 173(1): 182 - 194. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Filimonenko, S. Stuffers, C. Raiborg, A. Yamamoto, L. Malerod, E. M.C. Fisher, A. Isaacs, A. Brech, H. Stenmark, and A. Simonsen Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease J. Cell Biol., November 5, 2007; 179(3): 485 - 500. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Duffy, R. K. Peach, and E. A. Strand Progressive Apraxia of Speech as a Sign of Motor Neuron Disease Am J Speech Lang Pathol, August 1, 2007; 16(3): 198 - 208. [Abstract] [Full Text] [PDF]
|
|