Neurodegenerative disease/disorder

Melatonin secretion is synchronized to the light/dark (LD) cycle, with a nocturnal maximum (in young humans, about 200 pg/ml plasma) and low diurnal baseline levels (about 10 pg/ml plasma). Studies have supported the value of the exogenous administration of melatonin in circadian rhythm sleep disorders, insomnia, cancer, neurodegenerative diseases, disorders of the immune function, and oxidative damage (Karasek et al. 2002 Pandi-Perumal et al. 2005, 2006 Srinivasan et al. 2005a,b, 2006 Hardeland et al. 2006). 

Cell therapy, however, remains the most compelling treatment for neurodegenerative diseases, disorders, and injuries, including Parkinson s disease, Huntington s disease, traumatic brain injury, and stroke. 

The machinery involved in what could be considered the initiation point is probably quite specific for each neurodegenerative disorder. On the contrary, it is largely believed that neurodegenerative diseases have in common several molecular components of the machinery involved in the later phase of cell death execution. 

In many crucial biological processes, such as oxygen transport, electron transport, intermediary metabolism, metals play an important part. Therefore, disorders of metal homeostasis, metal bioavailability or toxicity caused by metal excess, are responsible for a large number of human diseases. We have already mentioned disorders of iron metabolism (see Chapter 7) and of copper metabolism (see Chapter 14). The important role, particularly of redox metals such as copper and iron, and also of zinc, in neurodegenerative diseases, such as Parkinson s disease, Alzheimer s disease, etc. has also been discussed (see Chapter 18). We will not further discuss them here. 

In this section, we will more particularly detail two neurodegenerative diseases for which GBP loss of function has clearly been reported by several studies and in which a therapeutic strategy based on resetting acetylation levels has been tested in vivo Polyglutamine disorders and Amyotrophic lateral sclerosis (ALS). 

It shows significant activity against a spectmm of neurodegenerative disorders in animal models that replicate many of the features of important human neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Parkinson s disease [147]. 

Only a small amount of aluminum is absorbed, and is usually readily eliminated in the urine, unless renal function is impaired. Then absorbed Ap+ can contribute to osteoporosis, encephalopathy, and proximal myopathy. There is some concern that excess of aluminium may contribute to the development of Alzheimer s disease and other neurodegen-erative disorders. 

A number of neurodegenerative disorders are characterized by neuronal damage that is induced by neurotoxic, aggregation-prone proteins. Various neurodegenerative diseases, including Alzheimer s disease ( caused by [l-amyloid deposits), prion disease... 

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