Sclerosis, amyotrophic lateral

Keywords Adaptive immune system ALS Chemokines Cytokines Innate Immune System Microglia Neuroinflammation 

In padents with bulbar involvement, symptoms of hoarseness, slurred speech, and drooling most often precede evidence 

The history and physical examinadon provide the founda-don for the diagnosis and should clemonsdate the combina-don of lower motor neuron (LMN) involvement, manifested by weakness and muscle adophy, and upper motor neuron (UMN) involvement, evidenced by increased tone and hyper-reflexia, in at least three areas, including the limbs, tongue, and back muscles. Needle EMG and nerve conduedon studies should be performed to confirm the diagnosis in all padents with suspected ALS. 

Unfortunately, efforts to halt the progression of disease wdth therapies targeted to these proposed mechanisms of disease have shown extremely modest benefits, at best. It is not that these mechanisms are not involved, but perhaps each individual mechanism may reflect only a limited aspect of the complex pathobiology of disease. Furthermore, most studies focus solely on the neuron and fail to consider the relevance of neuronal-glial interactions. What may be missing is that neuronal injury and cell death do not occur in isolation, but may require the participation of non-neuronal cells such as microglia and astrocytes, as well as other immune cells. 

Neuroinflammation is a significant aspect of the neuropathology of ALS, although it is not clear whether the inflammatory cells are the cause or the consequence of motor neuron injury. Inflammatory cells and mediators are present in the vicinity of degenerating motor neurons, and recent studies have suggested that these constituents may, in fact, contribute to motor neuron injury in ALS. 

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In summary, the steadily increasing size of geriatric populations in developed countries and the resultant increases in age-related diseases of the brain have provided the impetus for intensive study of the processes underlying neurodegeneration. A better understanding of these processes will likely lead to better methods of treatment not only for progressive memory disorders such as Alzheimer disease, but also for motor disorders such as amyotrophic lateral sclerosis, and cerebrovascular disorders such as stroke. 

Sendtner M (1999) Neurotrophic factors and amyotrophic lateral sclerosis. Handbook of exp pharmacol. 134 81-117... 

CD C14 C14.010 Caspase-9 Potential drug target for amyotrophic lateral sclerosis... 

Amyloid Precursor Protein Amyotrophic Lateral Sclerosis (ALS)... 

Interest in superoxide dismutase has increased in recent years with the discovery that a mutation in the gene coding for SOD is linked to certain types of the neurodegenerative disease amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig s disease. Exactly how mutant forms of SOD are involved in ALS is a subject of intense research. 

Hoffman PM, Festoff BW et al (1985) Isolation of LAV/HTLV-III from a patient with amyotrophic lateral sclerosis. N Engl J Med 313(5) 324-325 Hoke A, Cornblath DR (2004) Peripheral neuropathies in human immunodeficiency virus infection. Suppl Clin Neurophysiol 57 195-210... 

A/J A Jackson inbred mouse strain ALP Anti-leukoprotease ALS Amyotrophic lateral sclerosis cAMP Cyclic adenosine monophosphate also known as adenosine 3, 5 -phosphate AM Alveolar macrophage AML Acute myelogenous leukaemia AMP Adenosine monophosphate AMVN 2,2 -azobis (2,4-dimethylvaleronitrile)... 

Lou Gehrig s disease (amyotrophic lateral sclerosis ALS) displays motor neuron deposits of hyperphosphorylated neurofilament subunits in the sporadic disease. Familial ALS, some 20% of all cases of ALS, involves dominant superoxide dismutase SOD1 mutants that can form (3-barrel aggregates [49-51]. 

The lack of zinc can also be a problem in biological systems and is responsible for disease states. For example, nitric oxide-dependent apoptosis can be induced in motor neurons by zinc-deficient SOD, and in some cases of amyotrophic lateral sclerosis, zinc-deficient SOD may participate in this type of oxidative mechanism involving nitric oxide.969 One form of hereditary human hair loss or alopecia was mapped to a specific gene and a mutation found in affected individuals. The gene encodes a single zinc finger transcription factor protein with restricted expression in the brain and skin.970 Zinc has been implicated in Alzheimer s via beta amyloid formation, and a role has been attributed for the cerebral zinc metabolism in the neuropathogenesis of Alzheimer s disease.971... 

Ciliary neurotrophic factor (CNTF) decreases naturally occurring and axotomy-induced cell death and has been evaluated as a treatment for neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS)... 

Neurotrophic factors Mainly conditions caused by/associated with neurodegeneration, including peripheral neuropathies, amyotrophic lateral sclerosis and neurodegenerative diseases of the brain... 

IGF I has recently been the focus of considerable interest due to its actions on motor neurons. It can prevent normal motor neuron cell death during development, reduce the loss of these cells following nerve injury and enhance axonal regeneration. In the adult, injection of IGF I results in sprouting of motor neuron terminals and increases the size of the neuromuscular junction. These and other studies suggest potential therapeutic applications of IGF I in several neurological diseases including amyotrophic lateral sclerosis and peripheral neuropathies. 

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