肌肉萎缩是 ALS 最显着的症状之一。 Kasaskies 和其他人的研究表明，ALS 患者必须摄入比可比较的健康人更多的卡路里。我们的网站有自己的卡路里计算器。

乌尔姆大学的 Johannes Dorst 及其同事对 64 名可能的、可能的或确诊的 ALS 患者进行了一项随机对照研究（超高热量食品补充剂在肌萎缩侧索硬化症 (ALS) 中的安全性和耐受性；TOLCAL-ALS 研究）。埃斯科里亚尔标准。患者被随机分为四组：

高热量脂肪补充剂（405 kcal/天，100% 脂肪）， 超高热量脂肪补充剂（810 kcal/天，100% 脂肪）， 一种超高热量、富含碳水化合物的补充剂（900 kcal/天，49% 碳水化合物） 没有任何补充的开放控制（OC）组。主要终点是耐受性。对患者进行了 4 周以上的随访。 胃肠道副作用在超高热量脂肪补充剂组中最常见（75.0%），而食欲不振在超高热量、富含碳水化合物的补充剂组中最常见（35.3%）。

干预期间，高热量脂肪补充剂组和超高热量脂肪补充剂组患者体重增加+0.9 kg/月。对照组患者体重持续下降（-0.5 kg/月）。

研究结果表明，高热量食品补充剂经常会导致 ALS 患者出现轻度至中度耐受性问题，最明显的是高脂肪补充剂中的胃肠道症状，以及高碳水化合物补充剂中的食欲不振。测试的所有三种高热量食品补充剂都适合增加体重。

Here is a report that more than twice as many Americans dying from Parkinson disease in 2019 (35,311) compared with 1999 (14,593). The study was published in the November 16, 2021, issue of Neurology.

Using data obtained from the National Vital Statistics System of the National Center for Health Statistics, the researchers calculated a total of 479,059 U.S. deaths from Parkinson disease between 1999 and 2019.

The age-adjusted death rate nearly double in 20 years, from 1999 to 2019. There was an average annual increase of 2.4% over the two decades.

Parkinson disease mortality increased significantly in all age groups, sexes, and racial and ethnic groups, as well as in urban and rural locations. There were, however, several notable differences within these categories. Mortality rates for men were twice those for women throughout the study period. Also, White individuals had higher mortality rates than people from other racial or ethnic groups which implies there is some genetic aspect.

The scientists speculate that that increased exposure to pesticides, herbicides, heavy metals, and air pollution, could raise Parkinson disease risk. However a doubling death rate would mean a rather obvious change in environment The scientists speculate that as people are living longer, thereby contributing to higher Parkinson disease incidence and mortality. Yet in US the life expectancy didn't increase during that period.

Most patients die with Parkinson’s Disease and not from it. The illnesses that kill most people are the same as those that kill people with PD. These are heart conditions, stroke and cancer. As we age we become increasingly aware that more than one bad thing can happen to our bodies.

La fonte musculaire est l'un des symptômes les plus frappants de la SLA (maladie de Charcot). Il y a des études par Kasaskies et d'autres, qui ont démontré que les patients SLA doivent ingérer beaucoup plus de calories que les personnes comparables qui sont en bonne santé . Notre site Web a son propre calculateur de calories.

Johannes Dorst et ses collègues de l'université d'Ulm, ont mené une étude contrôlée randomisée (Safety and Tolerability of Ultra-high-caloric Food Supplements in Amyotrophic Lateral Sclerosis (ALS) ; étude TOLCAL-ALS) chez 64 patients atteints de ou SLA définitive selon les critères d'El Escorial. Les patients ont été randomisés en quatre groupes :

• un complément lipidique hypercalorique (405 kcal/jour, 100% lipides),
• un complément lipidique ultra-hypercalorique (810 kcal/jour, 100% lipides),
• un complément hypercalorique riche en glucides (900 kcal/jour, 49% de glucides)
• un groupe de contrôle ouvert (OC) sans supplément. Le critère principal était la tolérance. Les patients ont été suivis pendant 4 semaines.

Au cours de l'intervention, les patients ont pris +0,9 kg/mois de poids corporel dans le groupe des suppléments gras hypercaloriques et le groupe des suppléments gras hypercaloriques. Les patients du groupe témoin ont continué à perdre du poids corporel (−0,5 kg/mois).

Les effets secondaires gastro-intestinaux étaient les plus fréquents dans le groupe des suppléments gras ultra-caloriques (75,0 %), tandis que la perte d'appétit était la plus fréquente dans le groupe des suppléments ultra-caloriques riches en glucides (35,3 %).

Les résultats suggèrent que les compléments alimentaires riches en calories provoquent fréquemment des problèmes de tolérance légers à modérés chez les patients atteints de SLA, notamment des symptômes gastro-intestinaux dans les suppléments riches en graisses et une perte d'appétit dans les suppléments riches en glucides. Les trois compléments alimentaires hautement caloriques testés sont adaptés pour augmenter le poids corporel.

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Cet ouvrage (en Anglais) retrace les principaux acquis de la recherche sur la SLA au cours des 30 dernières années, présente les médicaments en essai clinique, ainsi que les recherches en cours sur les futurs traitements susceptibles de pouvoir stopper la maladie dans quelques années et d'apporter une guérison complète en une ou deux décennies.

Definitely since the beginning of the year, we have seen important publications in the neurodegenerative field. This concerns a fundamental aspect of research, rather than a clinical aspect.

Many age-related diseases, including Alzheimer's and Parkinson's, are caused by the aggregation of misfolded proteins that seem to be parked in the cytosol, instead of being shipped to where they should operate. The mechanisms underlying how aging causes protein aggregation are largely unknown.

Since protein synthesis is energetically expensive, the ribosome must balance the costs of efficiently manufacturing a protein with those of correctly folding it. When correctly folded, proteins perform their functions and remain soluble in the environment of the cell. However, larger proteins naturally have greater conformational variety, so the folding of these proteins requires tight control to ensure that the folding does not occur in one of multiple unproductive or misfolded pathways. cannot work properly and tend to stick to each other and other proteins, obstructing cellular processes and forming toxic aggregates.

Researchers at Stanford University have particularly studied the functioning of ribosomes and the influence of their dysfunction on the production of misfolded proteins.

In fact, the outer (cytosolic) face of the rough endoplasmic reticulum is dotted with ribosomes, but they are also found throughout the cytoplasm.

The role of the ribosome is to make new proteins. It does this by moving along a strand of messenger RNA and building a protein based on the code it reads. Making a protein this way is called translation. There are up to 10 million ribosomes in each cell.

Generating a functional proteome requires the ribosome to carefully regulate the disparate co-translational processes that determine the fate of nascent polypeptides. The non-uniform rate of translation elongation that defines translation kinetics appears to be the primary means of regulating this trade-off.

In new research published Jan. 19 in Nature, these researchers attributed this problem to a deficiency in the ribosomal machinery, which deficiency is age-related. Researchers in the lab of Judith Frydman, Donald Kennedy Professor of the Stanford School of Humanities, used two well-established models of human aging, yeast and roundworms. Aging modifies the elongation kinetics of translation in Caenorhabditis elegans and Saccharomyces cerevisiae.

Ribosome pausing was exacerbated at specific positions in yeast and aged worms, including polybasic stretch, resulting in increased ribosome collisions known to trigger ribosome-associated quality control (RQC). Notably, aged yeast cells exhibited impaired clearance and increased aggregation of RQC substrates.

Very small changes in folding efficiency with age will intensify in a vicious circle where translational defects lead to system overload, which in turn leads to increased protein aggregates with age which are themselves also toxic.

Décidément en début d'année, nous voyons arriver des publications importantes dans le domaine neurodégénératif. Celle ci concerne un aspect fondamental de la recherche, plutôt qu'un aspect clinique.

De nombreuses maladies liées à l'âge, y compris les maladies d'Alzheimer et de Parkinson, sont causées par l'agrégation des protéines mal repliées et qui semble parquées dans le cytosol, au lieu d'être expédiées là où elles devraient opérer. Les mécanismes sous-jacents à la façon dont le vieillissement provoque l'agrégation des protéines sont en grande partie inconnus.

La synthèse des protéines étant énergétiquement coûteuse, le ribosome doit équilibrer les coûts de fabrication efficace d'une protéine avec ceux de son repliement correct. Lorsqu'elles sont correctement repliées, les protéines remplissent leurs fonctions et restent solubles dans l'environnement de la cellule. Cependant les plus grandes protéines ont naturellement une plus grande variété conformationnelle, aussi le repliement de ces protéines nécessite un controle stricte pour garantir que le repliement ne se fasse pas dans l'une des multiples voies improductives ou mal repliées.Les protéines mal repliées, ne peuvent pas fonctionner correctement et ont tendance à se coller les unes aux autres et à d'autres protéines, obstruant les processus cellulaires et générant des agrégats toxiques.

Des chercheurs de l'Université de Stanford ont particulièrement étudié le fonctionnement des ribosomes et l'influence de leur dysfonctionnement sur la production de protéines mal repliés.

En fait la face externe (cytosolique) du réticulum endoplasmique rugueux est parsemée de ribosomes, mais on en trouve également dans tout le cytoplasme.

Le rôle du ribosome est de fabriquer de nouvelles protéines. Pour ce faire, il se déplace le long d'un brin d'ARN messager et construit une protéine basée sur le code qu'il lit. Faire une protéine de cette façon s'appelle la traduction. Il y a jusqu'à 10 millions de ribosomes dans chaque cellule.

La génération d'un protéome fonctionnel nécessite que le ribosome régule soigneusement les processus de co-traduction disparates qui déterminent le sort des polypeptides naissants. Le taux non uniforme d'allongement de la traduction qui définit la cinétique de la traduction apparaît comme le principal moyen de régulation de ce compromis.

Dans une nouvelle recherche publiée le 19 janvier dans Nature, ces chercheurs ont attribué ce problème à une déficience de la machinerie ribosomique, cette déficience étant liée à l'âge. Les chercheurs du laboratoire de Judith Frydman, titulaire de la chaire Donald Kennedy de la faculté des sciences humaines de Stanford, ont utilisé deux modèles bien établis du vieillissement humain, la levure et les vers ronds. Le vieillissement modifie la cinétique d'allongement de la traduction chez Caenorhabditis elegans et Saccharomyces cerevisiae.

La pause des ribosomes a été exacerbée à des positions spécifiques dans la levure et les vers âgés, y compris les étirements polybasiques, entraînant une augmentation des collisions de ribosomes connues pour déclencher le contrôle de la qualité associé aux ribosomes (RQC). Notamment, les cellules de levure âgées présentaient une clairance altérée et une agrégation accrue des substrats RQC.

De très légers changements dans l'efficacité du repliement avec l'âge s'intensifieront dans un cercle vicieux où les défauts de traduction conduisent à une surcharge du système, qui à son tour conduit à une augmentation des agrégats de protéines avec l'âge qui sont eux-mêmes également toxiques.

Paradoxically, the therapy that improves the quality of life of patients with Parkinson's disease is the one that later contributes to the decline in their quality of life. Indeed over time, L-dopa (l-3,4-Dihydroxyphenylalanine), the main treatment for Parkinson's disease, loses its effectiveness and causes involuntary muscle movements and erratic movements and sometimes hallucinations. Although this effect is well identified, scientists did not understand why L-dopa accelerates the progression of the disease.

L-dopa and other pharmacological treatments for Parkinson's disease are designed to replace lost dopamine caused by degenerating nerve cells in the brain. Although dopamine cannot cross the blood-brain barrier, which allows substances such as water and oxygen to pass into the brain, L-dopa can. However, 99% of L-dopa is metabolized outside the brain, so it is given in combination with an enzyme inhibitor to prevent side effects such as nausea and heart problems, and allow more of the drug remains in the blood so as to be percolated through the blood-brain barrier. In this case, 5 to 10% of the ingested dose reaches the brain.

A team of researchers from the University of California, Irvine studied the molecular binding characteristics of L-dopa and related compounds using an optical technology called surface plasmon resonance to measure interactions between the drug and the target proteins. The results of the study were recently published in ACS Chemical Neuroscience.

Their studies aimed to test whether continuous administration of L-dopa in animal models of Parkinson's disease is associated with increased iron accumulation in dopaminergic neurons in the brain and whether this accumulation depends on the binding of L-dopa to siderocalin.

The researchers also wanted to determine whether the complex can be detected in the blood of patients with Parkinson's disease. The relative amount of this complex would then serve as a biomarker to determine when it becomes appropriate to switch to new treatments for the disease.

Indeed l-DOPA chelates iron through its catechol group, is forming the l-DOPA:Fe complex. Siderophore-like catechol compounds are known to bind siderocalin (Scn)/lipocalin-2 to form stable siderophore:Fe:Scn complexes. Scn is up-regulated in the substantia nigra of PD patients and may play a role in the pathophysiology of PD.

Their results demonstrate that L-DOPA forms a stable complex with Scn in the presence of Fe3+.

Expressed more simply, this means that L-dopa and the protein siderocalin combine in the presence of iron to create a complex that can cause cellular iron overload, resulting in an imbalance between free radicals and antioxidants, as well as neuroinflammation.

The authors speculate that as Parkinson's disease progresses, this effect increases, inducing these negative side effects, while the dose needed to relieve disease symptoms increases, resulting in a window narrow therapy.

It remains that the effects of the enzyme inhibitor used to mitigate L-Dopa side effects, are not trivial either, but this study does not address this subject.

Moreover L-Dopa is not a panacea either, indeed its therapeutic effectiveness is different for different types of symptoms. Bradykinesia and rigidity are the most sensitive symptoms to L-Dopa administration, while tremors are less sensitive. Speech disorders, speech and swallowing disorders, postural instability and frozen gait are the least reactive symptoms.

Muscle wasting is one of the most striking symptoms of ALS. There were studies by Kasaskies and others, that demonstrated ALS patients have to ingest much more calories than comparable healthy persons. Our website has its own calorie calculator.

Johannes Dorst and colleagues from Ulm's university, conducted a randomised controlled study (Safety and Tolerability of Ultra-high-caloric Food Supplements in Amyotrophic Lateral Sclerosis (ALS); TOLCAL-ALS study) in 64 patients with possible, probable or definite ALS according to El Escorial criteria. Patients were randomised into four groups:

• a high-caloric fatty supplement (405 kcal/day, 100% fat),
• an ultra-high-caloric fatty supplement (810 kcal/day, 100% fat),
• an ultra-high-caloric, carbohydrate-rich supplement (900 kcal/day, 49% carbohydrates)
• an open control (OC) group without any supplement. The primary endpoint was tolerability. Patients were followed up over 4 weeks.

Gastrointestinal side effects were most frequent in the ultra-high-caloric fatty supplement group (75.0%), while loss of appetite was most frequent in the ultra-high-caloric, carbohydrate-rich supplement group (35.3%).

During intervention, patients gained +0.9 kg/month of body weight in the high-caloric fatty supplement group and the ultra-high-caloric fatty supplement group. Patients in the controlled group continued to lose body weight (−0.5 kg/month).

The findings suggest that high-caloric food supplements frequently cause mild to moderate tolerability issues in patients with ALS, most notably gastrointestinal symptoms in high-fat supplements, and loss of appetite in high-carbohydrate supplements. All three high-caloric food supplements tested are suited to increase body weight.

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This book retraces the main achievements of ALS research over the last 30 years, presents the drugs under clinical trial, as well as ongoing research on future treatments likely to be able stop the disease in a few years and to provide a complete cure in a decade or two.

Some neurodegenerative disorders are pathologically characterized by the deposition of abnormally aggregated proteins, both inside and outside the cells, in various peripheral tissues and the central nervous system (CNS). These diseases are called amyloidosis.

These amyloidogenic proteins are soluble in their healthy state. Yet under some unknown conditions, they can aggregate and form tertiary structures in crossed β sheets, ultimately leading to the onset of each disease. The pathological signs characteristic of Alzheimer's disease are two types of amyloid accumulation, each consisting of Aβ and tau.

Therefore, inhibition of amyloid protein aggregation or efficient clearance of already formed amyloids are considered promising therapeutic strategies. However, this strategy has so far been unsuccessful to improve cognition in Alzheimer's disease, so there is a need to investigate new ideas.

With the aim of treating Alzheimer's disease, scientists have studied the artificial addition of oxygen atoms to amyloid by a photooxygenation catalyst and photostimulation.

Oxygenated Aβ has the ability to inhibit the aggregation and clearance of Aβ in the brain. It was clarified that the clearance of oxygenated Aβ was improved and that microglia are involved in the mechanism. Similar experiments were performed with special attention to astrocytes as cells other than microglia in the brain, but no effect of improving the clearance of oxygenated Aβ was observed. This suggests the specific involvement of microglia.

Scientists have also attempted to develop a non-invasive photooxygenation method with the aim of adapting this method to humans. After developing a new photooxygenation catalyst with cerebral migration properties and performing a non-invasive reaction of intravenous administration of the catalyst and light irradiation from outside the skull, Aβ was able to be oxygenated in the brain of a mouse. alive.