Epigenetic Changes in Prion and Prion-like Neurodegenerative Diseases: Recent Advances, Potential as Biomarkers, and Future Perspectives

Hernaiz, Adelaida; Toivonen, Janne M.; Bolea, Rosa; Martín-Burriel, Inmaculada

doi:10.3390/ijms232012609

Cited by 13 publications

(4 citation statements)

References 239 publications

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“…As technology improves, more and more studies show that epigenetic mechanisms, such as DNA methylation, histone post-translational modifications and microRNA-mediated post-transcriptional gene regulation, are involved in the pathogenesis of AD and thus influence the onset and progression of AD ( Hernaiz et al, 2022 ; van Zundert and Montecino, 2022 ).…”

Section: Key Mechanisms Of Altered Ahn In Alzheimer’s Diseasementioning

confidence: 99%

Mechanisms of abnormal adult hippocampal neurogenesis in Alzheimer’s disease

et al. 2023

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Alzheimer’s disease (AD) is a degenerative disease of the central nervous system, the most common type of dementia in old age, which causes progressive loss of cognitive functions such as thoughts, memory, reasoning, behavioral abilities and social skills, affecting the daily life of patients. The dentate gyrus of the hippocampus is a key area for learning and memory functions, and an important site of adult hippocampal neurogenesis (AHN) in normal mammals. AHN mainly consists of the proliferation, differentiation, survival and maturation of newborn neurons and occurs throughout adulthood, but the level of AHN decreases with age. In AD, the AHN will be affected to different degrees at different times, and its exact molecular mechanisms are increasingly elucidated. In this review, we summarize the changes of AHN in AD and its alteration mechanism, which will help lay the foundation for further research on the pathogenesis and diagnostic and therapeutic approaches of AD.

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Section: Key Mechanisms Of Altered Ahn In Alzheimer’s Diseasementioning

confidence: 99%

Mechanisms of abnormal adult hippocampal neurogenesis in Alzheimer’s disease

et al. 2023

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“…Биомаркеры БА и когнитивных нарушений на основе исследования периферической крови и СМЖ продолжают интенсивно разрабатываться, классическими из них являются количественные показатели Aβ и тау-протеина. Также, в соответствии с результатами крупных когортных исследований, содержание патологических белков в плазме коррелирует с Aβ-нагрузкой, оцениваемой с помощью амилоидной ПЭТ [22]. Комбинация этих биомаркеров на основе исследования крови может предсказать начало БА, тем не менее они не являются определяющими диагностическими точками для оценки ответа на терапию, поскольку снижение отложения амилоида на ПЭТ не всегда связано с улучшением когнитивной функции [23].…”

Section:  болезнь альцгеймера как основная причина деменцииunclassified

Alzheimer Dementia as a Consequence of the Brain Glymphatic System Dysfunction

Широлапов,

Захаров,

Булгакова

et al. 2023

Психиатрия, Психотерапия И Клиническая Психология

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Определение основных патогенетических механизмов развития наиболее распространенной формы деменции – болезни Альцгеймера, а также поиск эффективных решений для замедления и прекращения прогрессирования заболевания относятся к одним из приоритетных направлений фундаментальной нейробиологии и практической медицины. Гипотеза бета-амилоида и тау-белка в значительной степени объясняет ключевые патологические особенности деменции альцгеймеровского типа. Системные механизмы и молекулярные процессы, вследствие которых такие белки накапливаются и приводят к прогрессированию заболевания, вызывают выраженный научный и практический интерес, что актуализировано сохранением терапевтического пробела в определении рациональных вмешательств, модифицирующих болезнь, а также поиском доступных биомаркеров, высокоинформативных на доклинической стадии нейродегенеративных расстройств и у людей без когнитивных нарушений и определяемых клинических симптомов. Тем не менее недавнее открытие аквапорин-зависимого глимфатического пути, управляющего центральным клиренсом растворенных веществ в головном мозге, выявило новый механизм, лежащий в основе патогенеза и прогрессирования нейродегенерации и нейровоспаления. Настоящий обзор представляет и систематизирует современные данные о причинно-следственных связях дисфункции глимфатической системы мозга и накопления патологических белков с недостаточным выведением токсических продуктов метаболизма из функционального пространства нейронов, являющихся ключевыми звеньями в развитии деменции альцгеймеровского типа. Determination of the main pathological mechanisms of the development of the most common form of dementia – Alzheimer’s disease, as well as the search for effective solutions to slow down and stop the progression of the disease, is one of the priority areas of fundamental neurobiology and practical medicine. The beta-amyloid and tau hypothesis largely explains the key pathological features of Alzheimer’s dementia. Systemic mechanisms and molecular processes, due to which such proteins accumulate and lead to the progression of the disease, are of great scientific and practical interest, which is updated by the persistence of a therapeutic gap in the definition of rational disease-modifying interventions, as well as by the search for available biomarkers that are highly informative at the preclinical stage of neurodegenerative disorders and in people without cognitive dysfunction. However, the recent discovery of an aquaporin-dependent glymphatic pathway that controls central solute clearance in the brain has revealed a new mechanism underlying the pathogenesis and progression of neurodegeneration and neuroinflammation. This review presents and systematizes current data on causal relationships between dysfunction of the glymphatic system of the brain and the accumulation of pathological proteins with insufficient excretion of toxic metabolic products from the functional space of neurons, which are key links in the development of dementia of the Alzheimer’s type.

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“…Although recent studies have shed light on the possible roles of DNA methylation in the pathogenesis of prion diseases [ 24 , 25 , 31 , 32 , 33 ], knowledge in this field is still scarce. Little is known about how 5mC patterns and DNA methylation enzymes behave throughout the course of these diseases and, to the best of our knowledge, no study has yet explored the role of 5hmC in prion pathology.…”

Section: Introductionmentioning

confidence: 99%

5-Methylcytosine and 5-Hydroxymethylcytosine in Scrapie-Infected Sheep and Mouse Brain Tissues

Hernaiz

Sentre

Betancor

et al. 2023

IJMS

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Scrapie is a neurodegenerative disorder belonging to the group of transmissible spongiform encephalopathies or prion diseases, which are caused by an infectious isoform of the innocuous cellular prion protein (PrPC) known as PrPSc. DNA methylation, one of the most studied epigenetic mechanisms, is essential for the proper functioning of the central nervous system. Recent findings point to possible involvement of DNA methylation in the pathogenesis of prion diseases, but there is still a lack of knowledge about the behavior of this epigenetic mechanism in such neurodegenerative disorders. Here, we evaluated by immunohistochemistry the 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) levels in sheep and mouse brain tissues infected with scrapie. Expression analysis of different gene coding for epigenetic regulatory enzymes (DNMT1, DNMT3A, DNMT3B, HDAC1, HDAC2, TET1, and TET2) was also carried out. A decrease in 5mC levels was observed in scrapie-affected sheep and mice compared to healthy animals, whereas 5hmC displayed opposite patterns between the two models, demonstrating a decrease in 5hmC in scrapie-infected sheep and an increase in preclinical mice. 5mC correlated with prion-related lesions in mice and sheep, but 5hmC was associated with prion lesions only in sheep. Differences in the expression changes of epigenetic regulatory genes were found between both disease models, being differentially expressed Dnmt3b, Hdac1, and Tet1 in mice and HDAC2 in sheep. Our results support the evidence that DNA methylation in both forms, 5mC and 5hmC, and its associated epigenetic enzymes, take part in the neurodegenerative course of prion diseases.

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Epigenetic Changes in Prion and Prion-like Neurodegenerative Diseases: Recent Advances, Potential as Biomarkers, and Future Perspectives

Cited by 13 publications

References 239 publications

Mechanisms of abnormal adult hippocampal neurogenesis in Alzheimer’s disease

Mechanisms of abnormal adult hippocampal neurogenesis in Alzheimer’s disease

Alzheimer Dementia as a Consequence of the Brain Glymphatic System Dysfunction

5-Methylcytosine and 5-Hydroxymethylcytosine in Scrapie-Infected Sheep and Mouse Brain Tissues

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