https://pure.knaw.nl/ws/files/488196/14941_285_swaab.pdf

Brain aging and Alzheimer's disease: "Wear and tear" versus "use it or lose it."

Peptides derived from ACTH/MSH (melanocortins) exert trophic influences on central and peripheral nervous tissue. The influence of melanocortins during ontogeny, following neural damage, and in certain neurological diseases are reviewed, and possible clinical indications for melanocortin therapy are given. The capacity and possible pathophysiological mechanism for melanocortins to enhance functional recovery following peripheral nerve damage as measured by functional, histological, and electrophysiological test methods are discussed extensively. Structure—activity studies have shown that the neurotrophic potency is not related to corticotropic or immunosuppressant activity but resides in the ACTH4–10 sequence present in α- and s-MSH and ACTH. The stable ACTH4–9 analogue Org.2766 is also active. The peptides are only effective if they are given during the first few days after injury, suggesting that they may be stimulating the initial sprouting response. We present evidence that MSH-like peptides may be formed locally in response to injury and thus play a biologically significant role in the regulation of nerve regeneration.

A Rationale for the Use of Melanocortins in Neural Injury

Recent advances in neuroscience and molecular neurochemistry have substantially increased the knowledge of the neuropathobiology of senile dementia and Alzheimer's disease. On the basis of various hypotheses concerning degenerative processes in aging brains, new therapeutic strategies have been developed, including nootropic drugs with different mechanisms of action and heterogenous chemical structures. Mutual relationships exist between neuroscientific research and nootropic drug development. To date, such areas of research and drug development have involved deficits of brain neurotransmission (cholinergic, monoaminergic, peptidergic), free radical-induced damage, disturbances of calcium homeostasis and excitatory amino acid function, and deposition of amyloid protein.

Neuropathobiology of senile dementia and mechanism of action of nootropic drugs.

https://dspace.library.uu.nl/bitstream/handle/1874/15841/gelijns_87_future.pdf;sequence=1

Future health care applications resulting from progress in the neurosciences: The significance of neural plasticity research

Brain aging is often considered in terms of a reduced neural plasticity. Commonly, the term neural plasticity is used to describe the adaptive capacity of the nervous system. It is now recognized that this adaptive capacity plays a key role in the development of specific neuronal networks and in the response to trauma or intoxication. Furthermore, it has been shown that dynamic adaptive changes at the synapse may lead to totally different communication patterns, resulting in an altered output of the brain. Neural plasticity can be studied at the molecular, morphological, neurophysiological, and the behavioral level and at all these levels specific age-related decreases in the adaptive capacity of the nervous system have been described (Swaab et al. 1986).

/pdf/nimodipine-and-neural-plasticity-1t1eh7tssi.pdf

Nimodipine and neural plasticity

Success in treating and preventing infection and vascular disease has led to a significant increase in the number of people over the age of 65. This increase in the elderly population has focused attention on normal changes of the aging brain and the chronic disorders that may develop during the aging process. Clearly, such disorders are not inevitable consequences of aging, but they are present to a greater extent in aged individuals. The two common conditions which fall into this category are parkinsonism and Alzheimer’s disease. Both of these devastating diseases of the nervous system are degenerative disorders of unknown origin. In each, multiple etiologies, including viral or immunologic causes, have been implicated but never proven. Both conditions reflect pathologic changes in relatively limited pathways within the central nervous system. In Alzheimer’s disease and, to a much lesser extent, Parkinson’s disease, changes are noted which are known to occur in healthy older individuals. Thus, both conditions may represent accelerated aging of specific neuronal pathways. In order to understand the quantitative alterations in the brain of patients with these disorders, it is necessary to define the extent to which normal individuals demonstrate alterations in the number of neurons, in microscopic pathology, and in neurotransmitter metabolism during the aging process.

Y. Tomozawa

Papers

Trophic Factors in Brain Aging and Disease