%0 Journal Article
%T Altered Gene Expression, Mitochondrial Damage and Oxidative Stress: Converging Routes in Motor Neuron Degeneration
%A Luisa Rossi
%A Cristiana Valle
%A Maria Teresa Carr¨¬
%J International Journal of Cell Biology
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/908724
%X Motor neuron diseases (MNDs) are a rather heterogeneous group of diseases, with either sporadic or genetic origin or both, all characterized by the progressive degeneration of motor neurons. At the cellular level, MNDs share features such as protein misfolding and aggregation, mitochondrial damage and energy deficit, and excitotoxicity and calcium mishandling. This is particularly well demonstrated in ALS, where both sporadic and familial forms share the same symptoms and pathological phenotype, with a prominent role for mitochondrial damage and resulting oxidative stress. Based on recent data, however, altered control of gene expression seems to be a most relevant, and previously overlooked, player in MNDs. Here we discuss which may be the links that make pathways apparently as different as altered gene expression, mitochondrial damage, and oxidative stress converge to generate a similar motoneuron-toxic phenotype. 1. Introduction Motor neuron diseases (MNDs) are a rather heterogeneous group of diseases, with either sporadic or genetic origin or both, all characterized by the progressive degeneration of motor neurons. All MNDs are primarily axonopathies of the motor neurons in which neuromuscular synapses are early targets of damage and death of motor neurons probably occurs following loss of the neuromuscular junctions [1]. MNDs may manifest as weakness, atrophy of muscles, difficulty in breathing, speaking, and swallowing, with symptoms and severity varying as a consequence of the different involvement of upper or lower motor neurons or both. The most common and studied form in adults is Amyotrophic Lateral Sclerosis (ALS), followed by Progressive Bulbar Palsy (PBP), the rarer forms being Progressive Muscular Atrophy (PMA) and Primary Lateral Sclerosis (PLS). These conditions seem to form a continuum of diseases since only part of patients have a ˇ°pureˇ± phenotype, while others with PBP or PLS eventually develop the widespread symptoms common to ALS [2]. In all these MNDs, onset of symptoms occurs mainly in people aged 40¨C70. Life expectancy is between 2 to about 5 years after onset in ALS and 6 months to 3 years in PBP, while pure PLS patients may have a normal or near-to-normal life duration. MNDs also include Spinal and Bulbar Muscular Atrophy (SBMA), in which age of onset and severity of manifestations vary from adolescence to old age, but longevity is usually not compromised. Infantile MNDs include Spinal Muscular Atrophy (SMA) with an infantile or juvenile onset and Lethal Congenital Contracture Syndrome (LCCS), causing prenatal death and thus
%U http://www.hindawi.com/journals/ijcb/2012/908724/