Neurodegenerative conditions

Each neurotrophic factor influences the growth and development of a specific group of neuronal types, with some cells being sensitive to several such factors. Many sustain specific neuronal populations whose death underlines various neurodegenerative diseases. This raises the possibility that these regulatory molecules may be of benefit in treating such diseases. Results from early clinical trials have been at best mixed, but many remain optimistic that neurotrophic factors may provide future effective treatments for some currently incurable neurodegenerative conditions. 

There are a number of findings suggesting that agents that facilitate elimination of protein carbonyls (by either proteolytic elimination or by enzymically mediated chemical reduction) may suppress neurodegenerative conditions in model systems (Botella et al., 2004). Consequently, as carnosine may also react with protein carbonyls, it is theoretically possible that it could suppress formation and /the reactivity of protein carbonyls in the brain. Whether carnosine participates in carbonyl reductase activity has not been investigated but it is also a reasonable speculation. 

Camosine s copper and zinc ion-chelating activity may also contribute to suppression of neurodegenerative conditions (Hipkiss, 2005). Zinc has been reported to be associated with the amyloid which accumulates in AD brain (Bush and Tanzi, 2002 Danscher et al, 1997 Religa et al, 2006), while copper ion-mediated oxidation of neuronal proteins may accompany both AD and PD (Smith et al., 2006). Carnosine has been found to protect cultured neurons against zinc-induced death (Kawahara et al,... 

Unlike the neurodegenerative conditions discussed above, diseases such as Alzheimer s and Parkinson s are underlined by the death of CNS neurons. Many of these cells respond to specific... 

FIGURE 4—16. Calcium may also rush into cells too quickly if its ion channels are opened too much, as is postulated to occur as a result of certain toxins, by stroke, or by neurodegenerative conditions (see Fig. 4—17). 

A limited form of excitotoxicity may be useful as a pruning mechanism for normal maintenance of the dendritic tree (see Fig. 1—23), getting rid of cerebral dead wood like a good gardener however, excitotoxicity to an excess is hypothesized to cause various forms of neurodegeneration, ranging from slow, relentless neurodegenerative conditions such as schizophrenia and Alzheimer s disease to sudden, catastrophic neuronal death such as stroke (Fig. 10—26). 

This disease develops when an abnormal prion protein present in the cadaveric material induces a cascade of conformational changes in host protein. Creutzfeldt-Jakob disease in recipients of somatropin differs from the sporadic form, in that it usually presents with cerebellar signs rather than cognitive impairment, and also in the prominence of prion protein amyloid plaques in nervous tissue (18). In a review, 139 cases of Creutzfeldt-Jakob disease were identified worldwide in people treated with cadaveric somatropin before recombinant human growth hormone became available in the mid-1980s (19). The prevalence of this fatal neurodegenerative condition in recipients of somatropin ranges from 0.3% in the USA to 4.4% in France. Creutzfeldt-Jakob disease has been reported to start at 4-30 years after therapy with cadaveric somatropin (18), so that further cases are anticipated and continue to be reported (20). 

A prolonged decrease in the stimulation of the postsy-naptic receptors can result in a functional increase in receptor sensitivity. The best example of this is the denervation supersensitivity seen when a peripheral nerve is severed.7 In this situation, the lack of presynaptic neurotransmitter release results in a compensatory increase in postsynaptic receptor numbers on the muscle cell. Similarly, the loss of the endogenous neurotransmitter dopamine in neurodegenerative conditions such as Parkinson disease can result in supersensitivity of receptors for that neurotransmitter.14 This increased receptor sensitivity becomes problematic because administration of dopaminelike drugs can cause excessive or untoward responses (see Chapter 10).14... 

Theoretically, could be useful for any condition characterized by moderate overactivation of NMDA glutamate receptors (possibly neurodegenerative conditions or even bipolar disorder, anxiety disorders, or chronic neuropathic pain), but this is not proven... 

How can microglia] responses be modulated during neurodegenerative conditions ... 

Neuroprotection induced by CsA under certain neurodegenerative conditions can be attiibuted solely to... 

---