Elsevier

Medical Hypotheses

Volume 74, Issue 1, January 2010, Pages 118-119
Medical Hypotheses

A potential role for crystallization inhibitors in treatment of Alzheimer’s disease

https://doi.org/10.1016/j.mehy.2009.07.029Get rights and content

Summary

Melatonin is a hormone synthesized from the neurotransmitter serotonin and is found mainly in the pineal gland. Melatonin has been suggested to have several properties, acting both as an antioxidant and a neuroprotective agent. Melatonin synthesis decreases with age in all humans, but this decline is more pronounced in Alzheimer’s patients. In fact, melatonin inhibits the formation of β-amyloid protein. The mechanism responsible for this decline has not been fully elucidated, although it is known that the human pineal gland calcifies with age. Such calcification necessarily implies the existence of a tissue injury that, if not reabsorbed by the immune system, will act as heterogeneous nucleant for hydroxyapatite and will induce calcification. For this reason, it is hypothesized that a lack of inhibitors of calcium salt crystallization, such as pyrophosphate and phytate, will favor calcification. Therefore, the absence of crystallization inhibitors may be a risk factor for development of Alzheimer’s disease, and this hypothesis should be evaluated.

Introduction

Alzheimer’s disease is a neurodegenerative condition resulting in a progressive loss of mental function because of brain tissue deterioration. The causes of Alzheimer’s disease remain unknown and no scientific explanation has gained total acceptance. An early hypothesis was that the disease is caused by a reduction in the synthesis of the neurotransmitter acetylcholine. Support for this idea has not been forthcoming, because drugs used to treat cholinergic deficiencies have not been of assistance in Alzheimer’s disease patients.

A more recent hypothesis (propounded in 1991) suggested that the cause of Alzheimer’s disease was the abnormal accumulation of β-amyloid protein in the brain [1], [2], [3], [4], [5]. Such deposition has also been recently linked with dementia, including Alzheimer’s disease, and with metabolic disorders, particularly those of hyperglycemia and insulin resistance [6], [7].

Section snippets

Melatonin

Melatonin (N-acetyl-5-methoxytryptamine) is a hormone synthesized from tryptophan (via serotonin) and occurs mainly in the pineal gland. It has been postulated that melatonin has several properties, acting as an antioxidant [8], [9], [10], [11], a neuroprotective agent [12], [13], and a stabilizer of the circadian rhythm [14], [15]. Thus, melatonin is now considered to play an important role in aging processes.

Melatonin excretion decreases with age in all humans [16], [17], but this decline is

Hypothesis

As outlined above, the presence of lesions in the pineal gland, which may be attributable to different causes (old age, or exposure to cytotoxic materials or environmental contaminants), would result in development of calcification, the extent of which would increase with more severe injury, with lower concentrations of crystallization inhibitors (pyrophosphate and phytate) and/or with reduced ability of the immune system. Calcification of the pineal gland would lead to a loss of function,

Conclusion

Any pathological calcification in mammals, for example, cardiovascular calcification, calcinosis cutis, or calcium lithiasis, requires an inducer, usually a heterogeneous nucleant, to destabilize the surrounding fluid that is generally in a metastable state. To protect the body from such unwanted processes, natural crystallization inhibitors are present in the body that prevent or slow crystallization. If, in addition, pathological crystallization takes place in a cellular environment (within a

Conflict of interest statement

All authors declare that there are not any financial and personal relationships with other people or organisations that could inappropriately influence (bias) their work.

Acknowledgments

Financial support by Dirección General de Investigación (Proyecto CTQ2006-05640) and Gobierno de las Islas Baleares (PROGECIC-1C) is gratefully acknowledged.

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