Turkiye Klinikleri Journal of Medical Sciences

.: REVIEW
Alzheimer Hastalığında Monoaminerjik Sistem Değişiklikleri: Geleneksel Bir Derleme
Alterations of Monoaminergic Systems in Alzheimer's Disease: A Traditional Review
Raviye ÖZEN KOCAa, Z. Işık SOLAK GÖRMÜŞa, Hatice SOLAKb
aNecmettin Erbakan Üniversitesi Meram Tıp Fakültesi, Fizyoloji ABD, Konya, Türkiye
bKütahya Sağlık Bilimleri Üniversitesi Tıp Fakültesi, Fizyoloji ABD, Kütahya, Türkiye
Turkiye Klinikleri J Med Sci.
doi: 10.5336/medsci.2022-89011
Article Language: TR
Full Text
ÖZET
Alzheimer hastalığı (AH); karakteristik klinik ve patolojik özelliklere sahip, yaşla ilişkili, nörodejeneratif bir hastalıktır. AH'den kaynaklanan ölüm oranı, 2020 yılında koronavirüs hastalığı 2019 pandemisi ile daha da şiddetlenmiştir. En çok bilinen nöropatolojik bulgular; ekstranöronal senil plaklar ve intranöronal nörofibriler yumaklardır. AH, monoaminerjik sistemleri de içeren birçok nöronal yapıyı etkileyen multisistemik bir hastalıktır. AH fizyopatolojisi ile nörotransmitterlerde meydana gelen fonksiyonel değişiklikler yakından ilişkilidir. Nöronal sinapsların kaybı ve nöron ölümü sonucunda asetilkolin gibi birçok nörotransmitterin azaldığı bilinmektedir. AH'de monoaminerjik sistemde temel olarak, dopaminerjik innervasyonu sağlayan substansia nigra çekirdeği, serotonerjik innervasyonu sağlayan dorsal rafe çekirdeği ve noradrenerjik innervasyonu sağlayan lokus seruleus çekirdeği, histaminerjik innervasyonu sağlayan tüberomamiller çekirdek önemli dejenerasyona maruz kalmaktadır. Bu çekirdeklerden projeksiyon alan bölgelerde ilgili nörotransmitterlerin düzeylerinde değişiklikler olmaktadır. Kombine tedavi (bilişsel geliştirici tedaviler, nöropsikiyatrik semptomları tedavi eden ilaçlar, hastalığı modifiye edici tedaviler) Alzheimer hastalarında davranışsal anormallikleri azaltmak ve kognitif fonksiyonları etkili şekilde restore etmek için önemlidir. AH için oluşturulacak tedavi stratejileri, monoaminerjik sistemin arkasındaki moleküler mekanizmayı anlamayı gerektirmektedir. Bu geleneksel derleme ile AH'de monoaminerjik sistemde özellikle dopamin, noradrenalin, serotonin ve histamin mekanizmalarında meydana gelen değişiklikleri ayrıntılı bir şekilde tartışıp, bu konuda bir bakış açısı sunmayı hedefliyoruz. Sonuç olarak monoaminerjik sistemin sinyalizasyon mekanizmasının ve monoaminerjik reseptörlerin etkilerinin daha iyi anlaşılması için insanlarda ve hayvan modellerinde daha çok çalışma yapılması gerekmektedir. Böylece, AH için yeni tedavi stratejilerinin gelişimi hızlanacaktır.

Anahtar Kelimeler: Alzheimer hastalığı; monoaminerjik sistem; dopamin; noradrenalin; serotonin; histamin
ABSTRACT
Alzheimer's disease (AD) is an age-related, neurodegenerative disease with characteristic clinical and pathological features. The death rate from AD was exacerbated by the coronavirus disease 2019 pandemic in 2020. The most common neuropathological findings are extraneuronal senile plaques and intraneuronal neurofibrillary tangles. AD is a multisystemic disease that affects many neuronal structures, including monoaminergic systems. Functional changes in neurotransmitters are closely related to the pathophysiology of AD. It is known that many neurotransmitters such as acetylcholine decrease as a result of loss of neuronal synapses and neuronal death. In the monoaminergic system, basically, the substantia nigra nucleus providing the dopaminergic innervation, the dorsal raphe nucleus providing the serotonergic innervation, the locus ceruleus nucleus providing the noradrenergic innervation, and the tuberomamillar nucleus providing the histaminergic innervation are exposed to significant degeneration in AD. There are changes in the levels of relevant neurotransmitters in the regions projected from these nuclei. Combined therapy (cognitive enhancing treatments, drugs to treat neuropsychiatric symptoms, disease-modifying therapies) important to reduce behavioral abnormalities and effectively restore cognitive functions in AD patients. Treatment strategies for AD require understanding the molecular mechanism behind the monoaminergic system. With this traditional review, we aim to discuss in detail the changes that occur in the monoaminergic system, especially in dopamine, noradrenaline, serotonin and histamine mechanisms in AD, and present a perspective on this issue. As a result; more studies in humans and animal models are needed to better understand the signaling mechanism of the monoaminergic system and the effects of monoaminergic receptors. Thus, the development of new treatment strategies for AD will accelerate.

Keywords: Alzheimer's disease; monoaminergic system; dopamine; noradrenaline; serotonin; histamine

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