TY - JOUR
T1 - Non-cell autonomous toxicity in neurodegenerative disorders
T2 - ALS and beyond
AU - Ilieva, Hristelina
AU - Polymenidou, Magdalini
AU - Cleveland, Don W.
PY - 2009/12/14
Y1 - 2009/12/14
N2 - Selective degeneration and death of one or more classes of neurons is the defining feature of human neurodegenerative disease. Although traditionally viewed as diseases mainly affecting the most vulnerable neurons, in most instances of inherited disease the causative genes are widely - usually ubiquitously - expressed. Focusing on amyotrophic lateral sclerosis (ALS), especially disease caused by dominant mutations in Cu/Zn superoxide dismutase (SOD1), we review here the evidence that it is the convergence of damage developed within multiple cell types, including within neighboring nonneuronal supporting cells, which is crucial to neuronal dysfunction. Damage to a specific set of key partner cells as well as to vulnerable neurons may account for the selective susceptibility of neuronal subtypes in many human neurodegenerative diseases, including Huntington's disease (HD), Parkinson's disease (PD), prion disease, the spinal cerebellar ataxias (SCAs), and Alzheimer's disease (AD).
AB - Selective degeneration and death of one or more classes of neurons is the defining feature of human neurodegenerative disease. Although traditionally viewed as diseases mainly affecting the most vulnerable neurons, in most instances of inherited disease the causative genes are widely - usually ubiquitously - expressed. Focusing on amyotrophic lateral sclerosis (ALS), especially disease caused by dominant mutations in Cu/Zn superoxide dismutase (SOD1), we review here the evidence that it is the convergence of damage developed within multiple cell types, including within neighboring nonneuronal supporting cells, which is crucial to neuronal dysfunction. Damage to a specific set of key partner cells as well as to vulnerable neurons may account for the selective susceptibility of neuronal subtypes in many human neurodegenerative diseases, including Huntington's disease (HD), Parkinson's disease (PD), prion disease, the spinal cerebellar ataxias (SCAs), and Alzheimer's disease (AD).
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U2 - 10.1083/jcb.200908164
DO - 10.1083/jcb.200908164
M3 - Review article
C2 - 19951898
AN - SCOPUS:74049164709
SN - 0021-9525
VL - 187
SP - 761
EP - 772
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 6
ER -