Neurodegenerative process

Atterwill, C. K. (1989). Brain reaggregate cultures in netirotoxicological investigations Adap-tational and neurodegenerative processes following lesions. Mo/. Toxicol. 1, 489-502. 

There are multiple mechanisms known to underlie the neuronal cell damage associated with injury or disease that at least theoretically could be targeted for pharmaceutical intervention. Currently however, there is no clinically available therapeutic agent that can reliably protect the brain from progressive neurodegenerative processes for sustained periods. Due to the extensive amount of preclinical research that has been conducted in recent years, there is a basis for optimism, however, it appears likely that some of these approaches will result in clinically effective therapeutic modalities in the near future. A short overview of some of the investigational approaches to combat neurodegeneration appears below. 

Gelman BB, Wolf DA, Rodriguez-Wolf M et al (1997) Mononuclear phagocyte hydrolytic enzyme activity associated with cerebral HIV-1 infection. Am J Pathol 151 1437-1446 Giraudon P, Buart S, Bernard A et al (1997) Cytokines secreted by gUal cells infected with HTLV-I modulate the expression of matrix metalloproteinases (MMPs) and their natural inhibitor (TIMPs) possible involvement in neurodegenerative processes. Mol Psychiatry 2(107-10) 84... 

Mechanisms from Cell to Brain 352 Neurodegenerative Diseases 353 Huntington s Disease 353 Parkinson s Disease 358 Perspectives on the Pharmacogenomics of Neurodegenerative Processes 361 Conclusions 362 References 363... 

It is now well established that a neurodegenerative pathway leading from soluble to insoluble, filamentous tau protein is central to the neurodegenerative process in the human tauopathies. The availability of animal models that exhibit the essential molecular and cellular features... 

Neurochemical imaging and MRS techniques have obvious, although longterm studies of neurochemistry in vivo have yet to be applied to schizophrenia. One correlate of the neurodegenerative process proposed in the NMDA receptor hypofunction hypothesis is demonstrated in the relationship between anterior cingulate NAA deficits and disease duration (Ende et al., 2000). A... 

Apparent perturbations of monoamine metabolism may arise as a consequence of an ongoing neurodegenerative process that results in the loss of dopamine- and/or serotonin-containing neurones. Such loss could therefore produce a CSF metabolite profile characteristic of one of the inborn errors of metabolism documented above. 

It thereby also metabolizes the amine most closely linked to control of blood pressure (norepinephrine). The B form is thought to convert some amine substrates, called protoxins, into toxins that may cause damage to neurons. Because of these observations, MAO A inhibition is linked both to antidepressant action and to the troublesome hypertensive side effects of the MAO inhibitors. Inhibition of MAO B is linked to prevention of neurodegenerative processes, such as those in Parkinson s disease. 

Similar to opioids, the cannabinoid system appears to be intricately involved in normal physiology, specifically in the control of movement, formation of memories, and appetite control. Basic research has discovered that members of this family of compounds have the capacity to protect threatened neurons, thereby slowing neurodegenerative processes that ultimately lead to physical disability. As the function of the physiological role of endocannabinoids becomes clearer, it appears the system may be involved in the pathology of several neurological diseases, specifically multiple sclerosis, spasticity, and pain. In 1999 the German journal, Forschende Komplementar-medizin und Klassische Naturheilkunde (Research in Complementary and Classical Natural Medicine) commented ... 

Alzheimer s disease (AD) is one of the most common forms of dementia that affect the elderly population. The histopathological hallmarks of AD are extracellular deposits known as neuritic amyloid plaques and intraneuronal inclusions composed of hyperphosphorylated tangles enriched with tau proteins.1 The principal component of the neuritic plaques is aggregation of amyloid (A0), which is likely to play a role in the neurodegenerative process. The relative contribution of the various forms (soluble dimers, small oligomers, protofibrils, and fibrils) of A0 to neuronal... 

Neuroinflammation emerges as a driving force in chronic neurodegenerative processes like Alzheimer s (AD) or Parkinson s disease (PD). Neuroinflammatoiy mediators such as cytokines, reactive oxygen species and molecules of the arachidonic acid pathway are generated and released by microglia, astrocytes and neurons upon stimulation and activation. In general, enhanced release of these substances has been considered to be detrimental. 

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