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Advances on the Neuroprotective Effect of Food and Natural Bioactive Compounds on Alzheimer

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (30 April 2020) | Viewed by 91758

Special Issue Editors

Special Issue Information

Dear Colleagues,

At present, there exists an ever-growing interest in the potential health benefits that some food/natural components may confer. Amongst the different bioactivities studied related to the consumption of health-promoting food/natural components, their possible neuroprotective effect is gaining importance due to the huge negative impact that neurodegenerative diseases (ND) have on society. Indeed, the possibility of finding some dietary/natural components, such as terpenes, alkaloids, carbohydrates, polyphenols, peptides, etc., able to positively prevent ND has evolved in a research line of great significance. However, to date, the mechanisms through which their neuroprotective activities would be exerted are still under discussion and in many cases largely unknown in several ND, especially in the case of Alzheimer’s disease (AD). At present, AD is considered an incurable disease and treatments are only focused on alleviating symptoms. For this reason, the prevention of the development of this disease is of utmost importance. In this regard, this Special Issue might be a very useful tool to discuss the neuroprotective effects of dietary/natural compounds at a molecular level against this pandemic illness. This Special Issue of International Journal of Molecular Sciences will contain both research and review papers by recognized experts in this field concerning various aspects related to the neuroprotective effect of food and natural bioactive compounds on different models of Alzheimer’s.

Prof. Dr. Alejandro Cifuentes
Prof. Dr. Elena Ibáñez
Guest Editors

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Related Special Issue

Published Papers (7 papers)

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Research

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12 pages, 1673 KiB  
Article
Synergistic Neuroprotective Effect of Schisandra chinensis and Ribes fasciculatum on Neuronal Cell Death and Scopolamine-Induced Cognitive Impairment in Rats
by Eunkuk Park, Min Jeong Ryu, Nam Ki Kim, Mun Hyoung Bae, Youngha Seo, Jeonghyun Kim, Subin Yeo, Memoona Kanwal, Chun Whan Choi, Jun Young Heo and Seon-Yong Jeong
Int. J. Mol. Sci. 2019, 20(18), 4517; https://doi.org/10.3390/ijms20184517 - 12 Sep 2019
Cited by 22 | Viewed by 3684
Abstract
Mild cognitive impairment (MCI) is considered as a transitional stage between aging and Alzheimer’s disease. In the present study, we examined the protective effect of Schisandra chinensis (SC) and Ribes fasciculatum (RF) on neuronal cell death in vitro and scopolamine-induced cognitive impairment in [...] Read more.
Mild cognitive impairment (MCI) is considered as a transitional stage between aging and Alzheimer’s disease. In the present study, we examined the protective effect of Schisandra chinensis (SC) and Ribes fasciculatum (RF) on neuronal cell death in vitro and scopolamine-induced cognitive impairment in Sprague Dawley® rats in vivo. A mixture of SC and RF extracts (SC+RF) significantly protected against hydrogen peroxide-induced PC12 neuronal cell death. The neuroprotective effect of SC+RF on scopolamine-induced memory impairment in rats was evaluated using the passive avoidance test and the Morris water maze test. In the passive avoidance test, SC+RF-treated rats showed an increased latency to escape, compared to the scopolamine-treated rats. Moreover, SC+RF treatment significantly reduced escape latency in water maze test, compared to treatment with scopolamine alone. To verify the long-term memory, we performed probe test of water maze test. As a result, rat treated with SC+RF spent more time in the target quadrant. Consistent with enhancement of memory function, the brain derived neurotrophic factor (BDNF) and its downstream molecules (pERK, pATK, and pCREB) are increased in SC+RF treatment in hippocampal area compared with scopolamine treated group. These results suggest that a mixture of SC and RF extracts may be a good therapeutic candidate for preventing mild cognitive impairment. Full article
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17 pages, 7403 KiB  
Article
Topographical Visualization of the Reciprocal Projection between the Medial Septum and the Hippocampus in the 5XFAD Mouse Model of Alzheimer’s Disease
by Sujin Kim, Yunkwon Nam, Yu-on Jeong, Hyun Ha Park, Seong-kyung Lee, Soo Jung Shin, Haram Jung, Byeong-Hyeon Kim, Sang Bum Hong, Yong Ho Park, Jihee Kim, Jaemin Yu, Doo-Han Yoo, Sun-Hyun Park, Seong Gak Jeon and Minho Moon
Int. J. Mol. Sci. 2019, 20(16), 3992; https://doi.org/10.3390/ijms20163992 - 16 Aug 2019
Cited by 23 | Viewed by 8453
Abstract
It is widely known that the degeneration of neural circuits is prominent in the brains of Alzheimer’s disease (AD) patients. The reciprocal connectivity of the medial septum (MS) and hippocampus, which constitutes the septo-hippocampo-septal (SHS) loop, is known to be associated with learning [...] Read more.
It is widely known that the degeneration of neural circuits is prominent in the brains of Alzheimer’s disease (AD) patients. The reciprocal connectivity of the medial septum (MS) and hippocampus, which constitutes the septo-hippocampo-septal (SHS) loop, is known to be associated with learning and memory. Despite the importance of the reciprocal projections between the MS and hippocampus in AD, the alteration of bidirectional connectivity between two structures has not yet been investigated at the mesoscale level. In this study, we adopted AD animal model, five familial AD mutations (5XFAD) mice, and anterograde and retrograde tracers, BDA and DiI, respectively, to visualize the pathology-related changes in topographical connectivity of the SHS loop in the 5XFAD brain. By comparing 4.5-month-old and 14-month-old 5XFAD mice, we successfully identified key circuit components of the SHS loop altered in 5XFAD brains. Remarkably, the SHS loop began to degenerate in 4.5-month-old 5XFAD mice before the onset of neuronal loss. The impairment of connectivity between the MS and hippocampus was accelerated in 14-month-old 5XFAD mice. These results demonstrate, for the first time, topographical evidence for the degradation of the interconnection between the MS and hippocampus at the mesoscale level in a mouse model of AD. Our results provide structural and functional insights into the interconnectivity of the MS and hippocampus, which will inform the use and development of various therapeutic approaches that target neural circuits for the treatment of AD. Full article
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11 pages, 1859 KiB  
Article
Preventive Effects of Tryptophan–Methionine Dipeptide on Neural Inflammation and Alzheimer’s Pathology
by Yasuhisa Ano, Yuka Yoshino, Kazuyuki Uchida and Hiroyuki Nakayama
Int. J. Mol. Sci. 2019, 20(13), 3206; https://doi.org/10.3390/ijms20133206 - 29 Jun 2019
Cited by 17 | Viewed by 4021
Abstract
Preventive approaches for age-related memory decline and dementia have become a high priority in the aging society because of the lack of therapeutic approaches. Recent epidemiological studies have reported that fermented dairy products can help prevent dementia. Previously, we identified tryptophan–tyrosine (WY) and [...] Read more.
Preventive approaches for age-related memory decline and dementia have become a high priority in the aging society because of the lack of therapeutic approaches. Recent epidemiological studies have reported that fermented dairy products can help prevent dementia. Previously, we identified tryptophan–tyrosine (WY) and tryptophan–methionine (WM) peptides as the suppressants of activation of the primary microglia and showed that WY peptide consumption suppresses inflammation in the brains of Alzheimer’s disease model mice. However, the effects of the WM peptide on inflammation in the brain and Alzheimer’s pathology have not been investigated. Here, we evaluated the effect of WM peptide consumption on Alzheimer’s disease model (5×FAD) mice. In 5×FAD mice, intake of WM peptide suppressed the production of inflammatory cytokines, activation of microglia, and infiltration of activated microglia around β amyloid (Aβ) depositions. WM peptide intake reduced Aβ deposition in the cortex and hippocampus and then improved the object recognition memory. Taken together with previous reports, the current findings indicate that ingestion of tryptophan-related peptides or food material rich in tryptophan-related peptides, thereby regulating microglial activity, represents a potential preventive approach for cognitive decline and dementia related to inflammation. Full article
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20 pages, 4021 KiB  
Article
Red Ginseng Attenuates Aβ-Induced Mitochondrial Dysfunction and Aβ-mediated Pathology in an Animal Model of Alzheimer’s Disease
by Soo Jung Shin, Seong Gak Jeon, Jin-il Kim, Yu-on Jeong, Sujin Kim, Yong Ho Park, Seong-Kyung Lee, Hyun Ha Park, Sang Bum Hong, Sua Oh, Ji-young Hwang, Hyeon soo Kim, HyunHee Park, Yunkwon Nam, Yong Yook Lee, Jwa-Jin Kim, Sun-Hyun Park, Jong-Seok Kim and Minho Moon
Int. J. Mol. Sci. 2019, 20(12), 3030; https://doi.org/10.3390/ijms20123030 - 21 Jun 2019
Cited by 46 | Viewed by 7416
Abstract
Alzheimer’s disease (AD) is the most common neurodegenerative disease and is characterized by neurodegeneration and cognitive deficits. Amyloid beta (Aβ) peptide is known to be a major cause of AD pathogenesis. However, recent studies have clarified that mitochondrial deficiency is also a mediator [...] Read more.
Alzheimer’s disease (AD) is the most common neurodegenerative disease and is characterized by neurodegeneration and cognitive deficits. Amyloid beta (Aβ) peptide is known to be a major cause of AD pathogenesis. However, recent studies have clarified that mitochondrial deficiency is also a mediator or trigger for AD development. Interestingly, red ginseng (RG) has been demonstrated to have beneficial effects on AD pathology. However, there is no evidence showing whether RG extract (RGE) can inhibit the mitochondrial deficit-mediated pathology in the experimental models of AD. The effects of RGE on Aβ-mediated mitochondrial deficiency were investigated in both HT22 mouse hippocampal neuronal cells and the brains of 5XFAD Aβ-overexpressing transgenic mice. To examine whether RGE can affect mitochondria-related pathology, we used immunohistostaining to study the effects of RGE on Aβ accumulation, neuroinflammation, neurodegeneration, and impaired adult hippocampal neurogenesis in hippocampal formation of 5XFAD mice. In vitro and in vivo findings indicated that RGE significantly improves Aβ-induced mitochondrial pathology. In addition, RGE significantly ameliorated AD-related pathology, such as Aβ deposition, gliosis, and neuronal loss, and deficits in adult hippocampal neurogenesis in brains with AD. Our results suggest that RGE may be a mitochondria-targeting agent for the treatment of AD. Full article
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Review

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40 pages, 2044 KiB  
Review
Dietary Polyphenols: A Multifactorial Strategy to Target Alzheimer’s Disease
by Sudip Dhakal, Naufal Kushairi, Chia Wei Phan, Benu Adhikari, Vikineswary Sabaratnam and Ian Macreadie
Int. J. Mol. Sci. 2019, 20(20), 5090; https://doi.org/10.3390/ijms20205090 - 14 Oct 2019
Cited by 64 | Viewed by 9032
Abstract
Ageing is an inevitable fundamental process for people and is their greatest risk factor for neurodegenerative disease. The ageing processes bring changes in cells that can drive the organisms to experience loss of nutrient sensing, disrupted cellular functions, increased oxidative stress, loss of [...] Read more.
Ageing is an inevitable fundamental process for people and is their greatest risk factor for neurodegenerative disease. The ageing processes bring changes in cells that can drive the organisms to experience loss of nutrient sensing, disrupted cellular functions, increased oxidative stress, loss of cellular homeostasis, genomic instability, accumulation of misfolded protein, impaired cellular defenses and telomere shortening. Perturbation of these vital cellular processes in neuronal cells can lead to life threatening neurological disorders like Alzheimer’s Disease, Parkinson’s Disease, Huntington’s Disease, Lewy body dementia, etc. Alzheimer’s Disease is the most frequent cause of deaths in the elderly population. Various therapeutic molecules have been designed to overcome the social, economic and health care burden caused by Alzheimer’s Disease. Almost all the chemical compounds in clinical practice have been found to treat symptoms only limiting them to palliative care. The reason behind such imperfect drugs may result from the inefficiencies of the current drugs to target the cause of the disease. Here, we review the potential role of antioxidant polyphenolic compounds that could possibly be the most effective preventative strategy against Alzheimer’s Disease. Full article
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19 pages, 1023 KiB  
Review
Ketogenic Diet in Alzheimer’s Disease
by Marta Rusek, Ryszard Pluta, Marzena Ułamek-Kozioł and Stanisław J. Czuczwar
Int. J. Mol. Sci. 2019, 20(16), 3892; https://doi.org/10.3390/ijms20163892 - 9 Aug 2019
Cited by 201 | Viewed by 42402
Abstract
At present, the prevalence of Alzheimer’s disease, a devastating neurodegenerative disorder, is increasing. Although the mechanism of the underlying pathology is not fully uncovered, in the last years, there has been significant progress in its understanding. This includes: Progressive deposition of amyloid β-peptides [...] Read more.
At present, the prevalence of Alzheimer’s disease, a devastating neurodegenerative disorder, is increasing. Although the mechanism of the underlying pathology is not fully uncovered, in the last years, there has been significant progress in its understanding. This includes: Progressive deposition of amyloid β-peptides in amyloid plaques and hyperphosphorylated tau protein in intracellular as neurofibrillary tangles; neuronal loss; and impaired glucose metabolism. Due to a lack of effective prevention and treatment strategy, emerging evidence suggests that dietary and metabolic interventions could potentially target these issues. The ketogenic diet is a very high-fat, low-carbohydrate diet, which has a fasting-like effect bringing the body into a state of ketosis. The presence of ketone bodies has a neuroprotective impact on aging brain cells. Moreover, their production may enhance mitochondrial function, reduce the expression of inflammatory and apoptotic mediators. Thus, it has gained interest as a potential therapy for neurodegenerative disorders like Alzheimer’s disease. This review aims to examine the role of the ketogenic diet in Alzheimer’s disease progression and to outline specific aspects of the nutritional profile providing a rationale for the implementation of dietary interventions as a therapeutic strategy for Alzheimer’s disease. Full article
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21 pages, 934 KiB  
Review
Mediterranean and MIND Diets Containing Olive Biophenols Reduces the Prevalence of Alzheimer’s Disease
by Syed Haris Omar
Int. J. Mol. Sci. 2019, 20(11), 2797; https://doi.org/10.3390/ijms20112797 - 7 Jun 2019
Cited by 50 | Viewed by 15594
Abstract
The risk of Alzheimer’s disease (AD) increases with nonmodifiable conditions including age and lack of effective efficacious pharmacotherapy. During the past decades, the non-pharmacotherapy mode of treatment of dietary modification received extensive attention in AD research. In order to reduce the AD pathology [...] Read more.
The risk of Alzheimer’s disease (AD) increases with nonmodifiable conditions including age and lack of effective efficacious pharmacotherapy. During the past decades, the non-pharmacotherapy mode of treatment of dietary modification received extensive attention in AD research. In order to reduce the AD pathology and cognitive decline, various dietary patterns have been attempted including caloric restriction (CR), dietary approaches to stop hypertension (DASH), ketogenic diets (KD), Mediterranean diet (MedDi) and Mediterranean-DASH diet Intervention for Neurological Delay (MIND) diet. Higher adherence to the MedDi diet was associated with decreases in cardiovascular and neurological disorders including AD and related cognitive decline. However, another emerging healthy dietary pattern MIND diet has also been associated with slower rates of cognitive decline and significant reduction of AD rate. Olive serves as one of the building block components of MedDi and MIND diets and the exerted potential health beneficial might be suggested due to the presence of its bioactive constituents such as oleic acids and phenolic compounds (biophenols). A few trials using medical food showed an optimal result in presymptomatic or early stages of AD. The review supports the notion that MedDi and MIND diets display potential for maintaining the cognitive function as nonpharmacological agents against AD pathology and proposed preventative mechanism through the presence of olive biophenols and presents the gaps along with the future directions. Full article
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