Neurodegeneration

An examination of the literature indicates that since 1982 the term neurodegeneration appears in the title of over 1280 indexed publications. Neurodegeneration is a mentioned topic of virtually all neurological science textbooks. Thus, it is safe to assume that the meaning of the word neurodegeneration is universally understood. Most relevant textbooks however will not actually define neurodegeneration but will discuss the issue in bits and pieces as part of the discussion of various diseases of the nervous system rather than as a single chapter. As previously discussed (Przedborski et al., 2003), neurodegeneration is composed of the prefix “neuro-,” which denotes relationship to a nerve or the nervous system (http:// tropmed.org/ dictionary/coverpage9.htm) and of “-degeneration,” which here is synonymous of devolution, meaning a process of declining from a higher to a lower level of effective power, vitality or essential quality (http://www.wordreference. com). Thus, neurodegeneration is any pathological condition in which the nervous system or nerve cell (i.e. neuron) loses its function, structure, or both. On a medical point of view however, the term neurodegeneration is used in a more restricted sense. Typically, it represents a large group of heterogeneous disorders in which affected neurons belong to specific subtypes, within specific anatomofunctional territories of the nervous system. Often, but not always, neurodegenerative diseases arise for unknown reasons and progress in a relentless manner. Within the context of this definition diseases of the nervous system can be catalogued into three broad categories: (i) pathologies which are restricted to the nervous system and which are primary neuronal diseases (i.e. neurodegenerative diseases per se); (ii) pathologies which are restricted to the nervous system but are not primary neuronal diseases, such as brain neoplasm or cerebral edema and hemorrhage; and (iii) pathologies provoked by systemic noxious factors which damage the nervous system, such cardiovascular arrest, poison, or infections. Based on this simple categorization, hundreds of disorders of the nervous system including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS) clearly fulfill the criteria of neurodegenerative disorder and are unanimously regarded as such. Aside from these unambiguous neurodegenerative diseases, others such as essential tremor, torsion dystonia, Tourette’s syndrome, or schizophrenia represent an interesting nosological challenge, as they do not show any distinct neuronal loss. Perhaps they have been traditionally included in this category because they are chronic diseases of the nervous system with an unknown cause. Finally, diseases such as multiple sclerosis (MS) also represent a perplexing situation. Conventionally, MS has been linked to pathology of the myelin that ensheath neuronal axons and not of the neuron per se. Several experts, however, have argued that MS is not only a demyelinating disease but also a disease where the neurons die due to a destruction of their axons. Worth noting, long-term disability in MS has a higher correlation with axonal damage than with the degree of demyelination (Bjartmar et al., 2003). For these reasons, several scientific authorities now regard MS as a neurodegenerative disease.