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New Insights Into the Pathogenesis of Bullous Pemphigoid: 2019 Update.
Genovese, G, Di Zenzo, G, Cozzani, E, Berti, E, Cugno, M, Marzano, AV
Frontiers in immunology. 2019;:1506
Abstract
There are several lines of evidence indicating that the physiopathological bases of bullous pemphigoid (BP), the most common subepidermal autoimmune bullous disease, are hallmarked by the production of autoantibodies directed against the hemidesmosomal anchoring proteins BP180 and BP230. In contrast to the robustness of the latter assumption, the multifaceted complexity of upstream and downstream mechanisms implied in the pathogenesis of BP remains an area of intense speculation. So far, an imbalance between T regulatory cells and autoreactive T helper (Th) cells has been regarded as the main pathogenic factor triggering the autoimmune response in BP patients. However, the contributory role of signaling pathways fostering the B cell stimulation, such as Toll-like receptor activation, as well as that of ancillary inflammatory mechanisms responsible for blister formation, such as Th17 axis stimulation and the activation of the coagulation cascade, are still a matter of debate. In the same way, the pathomechanisms implied in the loss of dermal-epidermal adhesion secondary to autoantibodies binding are not fully understood. Herein, we review in detail the current concepts and controversies on the complex pathogenesis of BP, shedding light on the most recent theories emerging from the literature.
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Advances in Management of Neuropsychiatric Syndromes in Neurodegenerative Diseases.
Cummings, J, Ritter, A, Rothenberg, K
Current psychiatry reports. 2019;(8):79
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Abstract
PURPOSE OF REVIEW Neuropsychiatric syndromes (NPS) are common in neurodegenerative disorders (NDD). This review describes the role of NPS in the diagnosis of NDD, criteria for the diagnosis of NPS, management of NPS, and agents in clinical trials for NPS. RECENT FINDINGS NPS play an increasingly important role in the diagnosis of NDD. Consensus diagnostic criteria have evolved for psychosis, depression, agitation, and apathy in NDD. With one exception-pimavanserin is approved for the treatment of hallucinations and delusions in Parkinson's disease-there are no drugs approved by the FDA for treatment of NPS in NDD. Trials show that atypical antipsychotics reduce psychosis in AD and in Parkinson's disease, although side effect concerns have constrained their use. Antidepressants show benefit in treatment of Parkinson's disease with depression. Several agents are in clinical trials for treatment of NPS in NDD. Neuropsychiatric syndromes play a major role in NDD diagnosis. Clinical criteria allow recognition of NPS in NDD. Psychotropic medications are often useful in the treatment of NPS in NDD; efficacious, safe, and approved agents are needed.
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Implications of Vitamin D in Multiple Sclerosis and Other Neurodegenerative Processes: Bibliometric Analysis and Systematic Review.
Caballero-Villarraso, J, Jiménez-Jiménez, MJ, Escribano, BM, Agüera, E, Santamaría, A, Túnez, I
CNS & neurological disorders drug targets. 2019;(6):478-490
Abstract
In recent years, numerous investigations focused on the pleiotropic actions of vitamin D have been carried out. These actions include the participation of this molecule in neurophysiological and neuropathological processes. As a consequence, abundant scientific literature on the role of this vitamin in neurodegenerative entities has emerged, even concerning clinical studies. To identify the level of scientific evidence concerning the relation between vitamin D and neurodegenerative diseases, from a quantitative and qualitative perspective. To describe, by means of a bibliometric analysis, the scientific production and its evolution through time in quantitative terms, regarding the implications of vitamin D in neurodegeneration. To analyse and present the degree of evidence in the aforementioned field of study, a systematic review of the literature focused on the most prevalent neurodegenerative diseases was carried out. We retrieved 848 articles in the bibliometric analysis, the majority of which were dated between the years 2010-2017. The most studied metabolite was the 25(OH)D3 and the most cited disease was multiple sclerosis. In the systematic review, we found studies about Alzheimer's and Parkinson's diseases and again, about multiple sclerosis prominently (in number and quality), with 12 randomised double-blind clinical trials. The research about vitamin D and its relations with neurodegenerative diseases shows a growing evolution over the last decade. More studies are needed to find correlations between the clinical severity of these diseases and the specific status of vitamin D and the genotypes related with them, which seems to be a future trend.
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Preventive and Therapeutic Effect of Ganoderma (Lingzhi) on Brain Injury.
Quan, Y, Ma, A, Yang, B
Advances in experimental medicine and biology. 2019;:159-180
Abstract
Neurological dysfunction and death are common events leading to acute and chronic neurodegenerative diseases. Neurodegenerative disorders such as Alzheimer's and Parkinson's disease account for a significant and increasing proportion of morbidity and mortality in the developed world. Ganoderma lucidum (G. lucidum, Lingzhi), one of highly nutritious and significantly effective medicinal herbs, has been used for clinical applications for thousands of years. Several researches have shown that it has a wide range of brain damage protection, such as amelioration of Alzheimer's disease, therapeutic effect on epilepsy, and the protective effect on neural cells in stroke injury. This chapter reviews the neuroprotective effects of G. lucidum and its extracts on brain injury diseases, including Alzheimer's disease, Parkinson's disease, stroke, epilepsy, and other neurodegenerative diseases, and the potential clinical applications.
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CpG and Non-CpG Methylation in the Diet-Epigenetics-Neurodegeneration Connection.
Fuso, A, Lucarelli, M
Current nutrition reports. 2019;(2):74-82
Abstract
PURPOSE OF REVIEW Unraveling the diet-epigenetics-neurodegeneration connection may disclose associated mechanisms and novel approaches to the neurodegenerative diseases. This review summarizes the basic concepts and the innovative results in this field focusing on the relevance of non-CpG methylation. RECENT FINDINGS Many multifactorial neurodegenerative diseases are associated with epigenetic changes, and the brain seems more prone to epigenetic changes than other tissues. Several environmental factors induce epigenetic modulation in the organisms: diet and nutrition retain a high capacity to modulate the epigenetic traits. Finally, unexpected, specific, and functional non-CpG methylation in the brain was identified. Non-CpG methylation modulates brain expression of genes especially in promoters characterized by low-density CpGs distribution. These genes appear more prone to the epigenetic effect of environmental factors, i.e., diet, possibly inducing neurodegenerative processes. Understanding these processes could help in setting nutritional intervention aimed at contrasting neurodegenerative diseases.
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Role of Flavonoids in Neurodegenerative Disorders with Special Emphasis on Tangeritin.
Fatima, A, Siddique, YH
CNS & neurological disorders drug targets. 2019;(8):581-597
Abstract
Flavonoids are naturally occurring plant polyphenols found universally in all fruits, vegetables and medicinal plants. They have emerged as a promising candidate in the formulation of treatment strategies for various neurodegenerative disorders. The use of flavonoid rich plant extracts and food in dietary supplementation have shown favourable outcomes. The present review describes the types, properties and metabolism of flavonoids. Neuroprotective role of various flavonoids and the possible mechanism of action in the brain against the neurodegeneration have been described in detail with special emphasis on the tangeritin.
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Vitamin D and the nervous system.
Bivona, G, Gambino, CM, Iacolino, G, Ciaccio, M
Neurological research. 2019;(9):827-835
Abstract
Objective: to summarise the activities that Vitamin D (VD) carries out in the brain and to clarify the potential role of VD in neurological diseases. Methods: a literature research has been performed in Pubmed using the following keywords: 'Vitamin D', 'nervous system', 'brain'. Results: the studies reviewed show that VD contributes to cerebral activity in both embryonic and adult brain, helping the connectivity of neural circuits responsible for locomotor, emotional and reward-dependent behavior. Low VD serum levels have been found in patients affected by Alzheimer Disease, Parkinson Disease, Multiple Sclerosis, Autism Spectrum Disorders, Sleep Disorders and Schizophrenia. Discussion: findings are controversial and should be interpreted with caution, since most of the studies performed have observational study set and few interventional studies are available, producing conflicting results. Overall, it can be stated that the potential role of Vitamin D in neurological diseases is mostly unclear and further randomised controlled trials are needed to understand better whether Vitamin D supplementation treatment can be useful in brain disorders.
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The Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) Diets Are Associated with Less Cognitive Decline and a Lower Risk of Alzheimer's Disease-A Review.
van den Brink, AC, Brouwer-Brolsma, EM, Berendsen, AAM, van de Rest, O
Advances in nutrition (Bethesda, Md.). 2019;(6):1040-1065
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Abstract
As there is currently no cure for dementia, there is an urgent need for preventive strategies. The current review provides an overview of the existing evidence examining the associations of the Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diets and their dietary components with cognitive decline, dementia, and Alzheimer's disease (AD). A systematic search was conducted within Ovid Medline for studies published up to 27 March 2019 and reference lists from existing reviews and select articles were examined to supplement the electronic search results. In total, 56 articles were included. Higher adherence to the Mediterranean diet was associated with better cognitive scores in 9 of 12 cross-sectional studies, 17 of 25 longitudinal studies, and 1 of 3 trials. Higher adherence to the DASH diet was associated with better cognitive function in 1 cross-sectional study, 2 of 5 longitudinal studies, and 1 trial. Higher adherence to the MIND diet was associated with better cognitive scores in 1 cross-sectional study and 2 of 3 longitudinal studies. Evidence on the association of these dietary patterns with dementia in general was limited. However, higher adherence to the Mediterranean diet was associated with a lower risk of AD in 1 case-control study and 6 of 8 longitudinal studies. Moreover, higher adherence to the DASH or MIND diets was associated with a lower AD risk in 1 longitudinal study. With respect to the components of these dietary patterns, olive oil may be associated with less cognitive decline. In conclusion, current scientific evidence suggests that higher adherence to the Mediterranean, DASH, or MIND diets is associated with less cognitive decline and a lower risk of AD, where the strongest associations are observed for the MIND diet.
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Omega-3 Fatty Acids and Neurodegenerative Diseases: New Evidence in Clinical Trials.
Avallone, R, Vitale, G, Bertolotti, M
International journal of molecular sciences. 2019;(17)
Abstract
A nutritional approach could be a promising strategy to prevent or slow the progression of neurodegenerative diseases such as Parkinson's and Alzheimer's disease, since there is no effective therapy for these diseases so far. The beneficial effects of omega-3 fatty acids are now well established by a plethora of studies through their involvement in multiple biochemical functions, including synthesis of anti-inflammatory mediators, cell membrane fluidity, intracellular signaling, and gene expression. This systematic review will consider epidemiological studies and clinical trials that assessed the impact of supplementation or dietary intake of omega-3 polyunsaturated fatty acids on neurodegenerative diseases such as Parkinson's and Alzheimer's diseases. Indeed, treatment with omega-3 fatty acids, being safe and well tolerated, represents a valuable and biologically plausible tool in the management of neurodegenerative diseases in their early stages.
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The intrinsic and extrinsic factors that contribute to proteostasis decline and pathological protein misfolding.
Kikis, EA
Advances in protein chemistry and structural biology. 2019;:145-161
Abstract
Proteostasis refers to the ability of cells to maintain the health of the proteome. Highly conserved quality control mechanisms exist to maintain proteostasis. These include the heat shock response, the unfolded protein response, and protein clearance/degradation pathways. Together, these mechanisms and others comprise the proteostasis network. This network is under constant assault and is strikingly sensitive to changes in the protein folding environment, resulting in proteostasis collapse under certain conditions. Here, the intrinsic and extrinsic stresses experienced by the proteostasis network are explored. The intrinsic stresses include genetic background as well as transcriptional and translational fidelity. These cause changes in the abundance or amino acid sequence of cellular proteins. Extrinsic stresses refer to environmental perturbation of the proteome, such as those caused by temperature stress, oxidative stress, air pollution and cigarette smoke. As the stress to the proteome exceeds the capacity of the proteostasis network, progressive neurodegenerative diseases of aging, such as Alzheimer's disease and Huntington's disease are more likely to ensue.