-
1.
NBIA Syndromes: A Step Forward from the Previous Knowledge.
Svetel, M, Dragašević, N, Petrović, I, Novaković, I, Tomić, A, Kresojević, N, Stanković, I, Kostić, V
Neurology India. 2021;(5):1380-1388
-
-
Free full text
-
Abstract
A disturbed iron metabolism may damage brain and trigger disorders known as neurodegeneration with brain iron accumulation (NBIA). NBIAs are rare, inherited disorders in which responsible mutations affect the function of proteins that participate in tissue iron homeostasis. Accumulated iron, which may be recognized as a low signal intensity on T2-weighted MRI images, oftentimes points to a diagnosis. Recent genetic discoveries confirm that NBIA is not a homogenous group of diseases. Fifteen different NBIAs have been described to date; among these, autosomal recessive inheritance was reported in 13, and autosmal dominant and X-linked dominant inheritance in one disease, respectively. Among NBIAs, the most common is pantothenate kinase-associated neurodegeneration (PKAN-NBIA 1) (30%-50% of all NBIA cases), that occurrs as a consequence of the autosomal recessive mutation in PANK2 gene, followed by phospholipase 2-associated neurodegeneration (PLAN, NBIA 2), due to mutation in PLA2G6 gene, and mitochondrial membrane protein-associated neurodegeneration (MPAN) with the underlying C19orf12 mutation [Table 1]. NBIAs are characterized by complex motor presentations from early-onset degeneration and premature fatality to adult-onset parkinsonism and dystonia. Epileptic seizures, pyramidal signs, visual disorders, and cognitive deterioration can develop. NBIAs are often refractory to therapeutical strategies, although certain interventions may provide significant symptomatic relief in selected patients. In this review, we discuss the expanding clinical spectrum of these complex and rare syndromes, their genetic and imaging features, and potential therapeutical targets and strategies.
-
2.
Essential Oils as a Potential Neuroprotective Remedy for Age-Related Neurodegenerative Diseases: A Review.
Abd Rashed, A, Abd Rahman, AZ, Rathi, DNG
Molecules (Basel, Switzerland). 2021;(4)
Abstract
Despite the improvements in life expectancy, neurodegenerative conditions have arguably become the most dreaded maladies of older people. The neuroprotective and anti-ageing potentials of essential oils (EOs) are widely evaluated around the globe. The objective of this review is to analyse the effectiveness of EOs as neuroprotective remedies among the four common age-related neurodegenerative diseases. The literature was extracted from three databases (PubMed, Web of Science and Google Scholar) between the years of 2010 to 2020 using the medical subject heading (MeSH) terms "essential oil", crossed with "Alzheimer's disease (AD)", "Huntington's disease (HD)", "Parkinson's disease (PD)" or "amyotrophic lateral sclerosis (ALS)". Eighty three percent (83%) of the studies were focused on AD, while another 12% focused on PD. No classifiable study was recorded on HD or ALS. EO from Salvia officinalis has been recorded as one of the most effective acetylcholinesterase and butyrylcholinesterase inhibitors. However, only Cinnamomum sp. has been assessed for its effectiveness in both AD and PD. Our review provided useful evidence on EOs as potential neuroprotective remedies for age-related neurodegenerative diseases.
-
3.
Miro (Mitochondrial Rho GTPase), a key player of mitochondrial axonal transport and mitochondrial dynamics in neurodegenerative diseases.
Panchal, K, Tiwari, AK
Mitochondrion. 2021;:118-135
Abstract
Miro (mitochondrial Rho GTPases) a mitochondrial outer membrane protein, plays a vital role in the microtubule-based mitochondrial axonal transport, mitochondrial dynamics (fusion and fission) and Mito-Ca2+ homeostasis. It forms a major protein complex with Milton (an adaptor protein), kinesin and dynein (motor proteins), and facilitates bidirectional mitochondrial axonal transport such as anterograde and retrograde transport. By forming this protein complex, Miro facilitates the mitochondrial axonal transport and fulfills the neuronal energy demand, maintain the mitochondrial homeostasis and neuronal survival. It has been demonstrated that altered mitochondrial biogenesis, improper mitochondrial axonal transport, and mitochondrial dynamics are the early pathologies associated with most of the neurodegenerative diseases (NDs). Being the sole mitochondrial outer membrane protein associated with mitochondrial axonal transport-related processes, Miro proteins can be one of the key players in various NDs such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD). Thus, in the current review, we have discussed the evolutionarily conserved Miro proteins and its role in the pathogenesis of the various NDs. From this, we indicated that Miro proteins may act as a potential target for a novel therapeutic intervention for the treatment of various NDs.
-
4.
[Evaluation of the impact of lockdown on the health and lifestyle of users of the Fundacio Esclerosi Multiple's neurorehabilitation centres in Lleida and Reus].
Zabay-Neiro, MC, Nieves-Collado, M, Carrés-Gonzalez, G, Curto-Estupiñà, G, Gargallo-Noval, M, Martínez-Lerín, N, Torres-Calvo, S, Yaya-Tur, G
Revista de neurologia. 2021;(7):249-257
Abstract
INTRODUCTION On 13 March 2020, a state of alarm was declared due to the COVID-19 pandemic, resulting in total lockdown in Spain. The neurorehabilitation centres of the Fundacio Esclerosi Multiple (FEM) provide care for people diagnosed with neuroprogressive diseases with significant health deficits. We look at how lockdown can affect their way of life. AIMS To assess and manage the impact of lockdown on persons with multiple sclerosis (MS) and other neurodegenerative diseases. PATIENTS AND METHODS Analytical observational study. An anonymous questionnaire was administered to all the patients undergoing comprehensive rehabilitation treatment at two of the FEM centres; the survey included questions on the demographic and clinical characteristics of the subjects, and an assessment of the impact of the pandemic on the physical, social and psychological spheres. RESULTS A total of 202 surveys were analysed. The average age of the participants was 49.09 years and 77.8% had MS, while 22.2% had other conditions. The most frequently reported physical symptoms were muscle weakness, loss of balance and fatigue. The study population remained active during lockdown. More than half of them did not report any increase in cognitive symptoms, but they did mention an increased sense of worry on an emotional level. CONCLUSIONS We can state that the actions deployed by the FEM to reduce the consequences of lockdown have been effective and have minimised the occurrence of maladaptive behaviours. The study has also opened the door for us to add new lines of intervention.
-
5.
Targeted pharmacotherapy against neurodegeneration and neuroinflammation in early diabetic retinopathy.
Rolev, KD, Shu, XS, Ying, Y
Neuropharmacology. 2021;:108498
Abstract
Diabetic retinopathy (DR), the most frequent complication of diabetes, is one of the leading causes of irreversible blindness in working-age adults and has traditionally been regarded as a microvascular disease. However, increasing evidence has revealed that synaptic neurodegeneration of retinal ganglion cells (RGCs) and activation of glial cells may represent some of the earliest events in the pathogenesis of DR. Upon diabetes-induced metabolic stress, abnormal glycogen synthase kinase-3β (GSK-3β) activation drives tau hyperphosphorylation and β-catenin downregulation, leading to mitochondrial impairment and synaptic neurodegeneration prior to RGC apoptosis. Moreover, glial cell activation triggers enhanced inflammation and oxidative stress, which may accelerate the deterioration of diabetic RGCs neurodegeneration. These findings have opened up opportunities for therapies, such as inhibition of GSK-3β, glial cell activation, glutamate excitotoxicity and the use of neuroprotective drugs targeting early neurodegenerative processes in the retina and halting the progression of DR before the manifestation of microvascular abnormalities. Such interventions could potentially remedy early neurodegeneration and help prevent vision loss in people suffering from DR.
-
6.
Overview of Beneficial Effects of (Poly)phenol Metabolites in the Context of Neurodegenerative Diseases on Model Organisms.
Carregosa, D, Mota, S, Ferreira, S, Alves-Dias, B, Loncarevic-Vasiljkovic, N, Crespo, CL, Menezes, R, Teodoro, R, Santos, CND
Nutrients. 2021;(9)
Abstract
The rise of neurodegenerative diseases in an aging population is an increasing problem of health, social and economic consequences. Epidemiological and intervention studies have demonstrated that diets rich in (poly)phenols can have potent health benefits on cognitive decline and neurodegenerative diseases. Meanwhile, the role of gut microbiota is ever more evident in modulating the catabolism of (poly)phenols to dozens of low molecular weight (poly)phenol metabolites that have been identified in plasma and urine. These metabolites can reach circulation in higher concentrations than parent (poly)phenols and persist for longer periods of time. However, studies addressing their potential brain effects are still lacking. In this review, we will discuss different model organisms that have been used to study how low molecular weight (poly)phenol metabolites affect neuronal related mechanisms gathering critical insight on their potential to tackle the major hallmarks of neurodegeneration.
-
7.
Deciphering the Role of Aberrant Protein Post-Translational Modification in the Pathology of Neurodegeneration.
Shafi, S, Singh, A, Gupta, P, Chawla, PA, Fayaz, F, Sharma, A, Pottoo, FH
CNS & neurological disorders drug targets. 2021;(1):54-67
Abstract
Neurodegenerative diseases, including Alzheimer's Disease (AD), Parkinson's Disease (PD), Amyotrophic Lateral Sclerosis (ALS) and Huntington's Disease (HD), are characterized by progressive neuronal dysfunction and death. Recent studies have established detrimental modifications in the structure and function of brain proteins, which stimulate their aggregation, misfolding and deposition in and around the neurons an important hallmark of neurodegenerative diseases. Post-Translational Modification (PTM) of proteins, including phosphorylation, acetylation, glycosylation, palmitoylation, SUMOylation, and ubiquitination, are important regulators of protein characteristics, including stability, intracellular distribution, activity, interactions, aggregation and clearance. Despite clear evidence that altered protein modifications emerging from impromptu chemical modifications to side chains of amino acid are associated with neurodegeneration, the underlying mechanisms that promote aberrant PTM remain poorly understood. Therefore, elucidating PTM of specific disease-associated proteins can prove to be a significant step in evaluating the functional alteration of proteins and their association with neurodegeneration. This review describes how aberrant PTM of various proteins is linked with the neurodegenerative disease pathogenesis, as well as molecular strategies targeting these modifications for treating such diseases, which are yet incurable.
-
8.
The redox language in neurodegenerative diseases: oxidative post-translational modifications by hydrogen peroxide.
Lee, YM, He, W, Liou, YC
Cell death & disease. 2021;(1):58
Abstract
Neurodegenerative diseases, a subset of age-driven diseases, have been known to exhibit increased oxidative stress. The resultant increase in reactive oxygen species (ROS) has long been viewed as a detrimental byproduct of many cellular processes. Despite this, therapeutic approaches using antioxidants were deemed unsuccessful in circumventing neurodegenerative diseases. In recent times, it is widely accepted that these toxic by-products could act as secondary messengers, such as hydrogen peroxide (H2O2), to drive important signaling pathways. Notably, mitochondria are considered one of the major producers of ROS, especially in the production of mitochondrial H2O2. As a secondary messenger, cellular H2O2 can initiate redox signaling through oxidative post-translational modifications (oxPTMs) on the thiol group of the amino acid cysteine. With the current consensus that cellular ROS could drive important biological signaling pathways through redox signaling, researchers have started to investigate the role of cellular ROS in the pathogenesis of neurodegenerative diseases. Moreover, mitochondrial dysfunction has been linked to various neurodegenerative diseases, and recent studies have started to focus on the implications of mitochondrial ROS from dysfunctional mitochondria on the dysregulation of redox signaling. Henceforth, in this review, we will focus our attention on the redox signaling of mitochondrial ROS, particularly on mitochondrial H2O2, and its potential implications with neurodegenerative diseases.
-
9.
The glycine betaine role in neurodegenerative, cardiovascular, hepatic, and renal diseases: Insights into disease and dysfunction networks.
Rosas-Rodríguez, JA, Valenzuela-Soto, EM
Life sciences. 2021;:119943
Abstract
Glycine betaine (N, N, N-trimethyl amine) is an osmolyte accumulated in cells that is key for cell volume and turgor regulation, is the principal methyl donor in the methionine cycle and is a DNA and proteins stabilizer. In humans, glycine betaine is synthesized from choline and can be obtained from some foods. Glycine betaine (GB) roles are illustrated in chemical, metabolic, agriculture, and clinical medical studies due to its chemical and physiological properties. Several studies have extensively described GB role and accumulation related to specific pathologies, focusing mainly on analyzing its positive and negative role in these pathologies. However, it is necessary to explain the relationship between glycine betaine and different pathologies concerning its role as an antioxidant, ability to methylate DNA, interact with transcription factors and cell receptors, and participate in the control of homocysteine concentration in liver, kidney and brain. This review summarizes the most important findings and integrates GB role in neurodegenerative, cardiovascular, hepatic, and renal diseases. Furthermore, we discuss GB impact on other dysfunctions as inflammation, oxidative stress, and glucose metabolism, to understand their cross-talks and provide reliable data to establish a base for further investigations.
-
10.
Prospective Role of Polyphenolic Compounds in the Treatment of Neurodegenerative Diseases.
Akter, R, Rahman, H, Behl, T, Chowdhury, MAR, Manirujjaman, M, Bulbul, IJ, Elshenaw, SE, Tit, DM, Bungau, S
CNS & neurological disorders drug targets. 2021;(5):430-450
Abstract
Aging is an important stage of the human life cycle and the primary risk factor for Neurodegenerative Diseases (ND). The aging process contributes to modifications in cells, which may lead to a lack of nutrient signaling, disrupted cellular activity, increased oxidative pressure, cell homeostasis depletion, genomic instability, misfolded protein aggregation, impaired cellular protection, and telomere reduction. The neuropathologies found in Alzheimer's Disease (AD) and Parkinson's Disease (PD) are internally and extrinsically compound environmental stressors which may be partially alleviated by using different phytochemicals. The new therapies for ND are restricted as they are primarily targeted at final disease progression, including behavioral shifts, neurological disorders, proteinopathies and neuronal failure. This review presents the role of phytochemicals-related polyphenolic compounds as an accompanying therapy model to avoid neuropathologies linked to AD, PD and to simultaneously enhance two stochastic stressors, namely inflammation and oxidative stress, promoting their disease pathologies. Therefore, this approach represents a prophylactic way to target risk factors that rely on their action against ND that does not occur through current pharmacological agents over the life of a person.