Title:Myopathic Involvement and Mitochondrial Pathology in Kennedy Disease and in Other Motor Neuron Diseases
Volume: 14
Issue: 5
Author(s): D. Orsucci, A. Rocchi, E. Caldarazzo Ienco, G. Alì, A. LoGerfo, L. Petrozzi, M. Scarpelli, M. Filosto, C. Carlesi, G. Siciliano, U. Bonuccelli and M. Mancuso
Affiliation:
Keywords:
ALS, AR, Kennedy’s disease, motoneuron disease, multiple deletions, mtDNA, SMA, SBMA.
Abstract: Kennedy disease (spinal and bulbar muscular atrophy, or SBMA) is a motor neuron disease caused
by a CAG expansion in the androgen-receptor (AR) gene. Increasing evidence shows that SBMA may have a
primary myopathic component and that mitochondrial dysfunction may have some role in the pathogenesis of
this disease. In this article, we review the role of mitochondrial dysfunction and of the mitochondrial genome
(mtDNA) in SBMA, and we present the illustrative case of a patient who presented with increased CK levels
and exercise intolerance. Molecular analysis led to definitive diagnosis of SBMA, whereas muscle biopsy
showed a mixed myopathic and neurogenic process with “mitochondrial features” and multiple mtDNA
deletions, supporting some role of mitochondria in the pathogenesis of the myopathic component of Kennedy
disease. Furthermore, we briefly review the role of mitochondrial dysfunction in two other motor neuron
diseases (namely spinal muscular atrophy and amyotrophic lateral sclerosis). Most likely, in most cases
mtDNA does not play a primary role and it is involved subsequently. MtDNA deletions may contribute to the
neurodegenerative process, but the exact mechanisms are still unclear. It will be important to develop a better
understanding of the role of mitochondrial dysfunction in motoneuron diseases, since it may lead to the
development of more effective strategies for the treatment of this devastating disorder
