Contrary to appearances, there is some links in this post with neurodegenerative diseases. Alcoholic liver injury are one kind of cellular stress. All drugs that can treat cellular stress, and especially Endoplasmic Reticulum (ER) stress, can probably be used against most common neurodegenerative diseases. The same is true for drugs with free radicals scavenging activity.

Euscaphis konishii Hayata is a traditional medicinal plant in China, and its leaves are usually used to make dishes for hepatic or gastrointestinal issues by Chinese She nationality. Hepatocellular carcinoma (hepatoma) is the most common type of primary liver cancer in adults. Hepatocellular carcinoma causes 662,000 deaths worldwide per year about half of them in China.

Pharmacological analysis showed that E. konishii leaves contain high levels of flavonoids and chromones with favorable anti-hepatoma effect. 8 flavonoids and 2 chromones were recognized in the chromone-rich extract. Chromones are found throughout the plant kingdom, where they serve as essential components of a number of structural polymers, provide protection from ultraviolet light, defend against herbivores and pathogens, and also mediate plant-pollinator interactions as floral pigments and scent compounds.

Alcohol-fed mice disease model were used to assess the hepatoprotective effects of these chromone-rich extract.

Chromone-rich extract represented strong free radicals scavenging activity in vitro. With oral administration, chromone-rich extract dose-dependently decreased the serum levels of alanine aminotransferase, alkaline phosphatase and aspartate aminotransferase in alcohol-fed mice.

Chromone-rich extract gradually increased the activity of superoxide dismutase and glutathione peroxidase in the alcohol-treated liver tissues. Chromone-rich extract also alleviated the hepatic inflammation, inhibited the hepatocyte apoptosis and lessened the alcohol-induced histological alteration and lipid accumulation in the liver tissues.

Chromone-rich extract administration inhibited the overexpression of endoplasmic reticulum chaperones signaling and unfolded protein response pathways to defense the ER-induced apoptosis. Pretreatment with chromone-rich extract also restored the mitochondrial membrane potentials andadenosine triphosphate levels, which in turn suppressed the Cytochrome C release and mitochondria-induced apoptosis.

Chromone-rich extract conferred great protection against alcoholic liver injury, which might be associated with its viability through suppressing reactive oxygen species stress and hepatocyte apoptosis.

It may be possible they also have positive effects in neurodegenerative diseases.

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What's in a name? Is Flail leg syndrome a variant of ALS or another disease? There are many anomalies in medicine, for example cancer sufferers in Western Europe could have a much different life expectancy when moving abroad, even when the new country is very similar to the country of origin.

It's a bit similar in ALS, it looks like ALS is not exactly the same disease in US, EU or Asia. Sometimes there is a understandable reason for example the statistical frequency of SOD1 mutations is different in Asia from US. Sometimes it is simply a matter of different semantics, some neurologists tell ALS is both upper and lower motor neurons, others have different opinions.

"Flail leg syndrome" is a Asian variant of amyotrophic lateral sclerosis with the characteristics of slow progression and the symptoms confined to the lumbosacral region for extended periods. In US it would have probably been called "Progressive Muscular Atrophy".

Yet there is no genetic background behind Flail leg syndrome, so why is it a regional appellation? In this new publication the scientists astonishingly decided that a slow progressing disease must be called "Flail leg syndrome".

The objective of a new study was to determine a cutoff time of disease progression that could differentiate Flail leg syndrome from the typical lower limb onset Amyotrophic Lateral Sclerosis.

A cutoff point analysis was performed with maximally selected log-rank statistics in patients with lower limb onset Amyotrophic Lateral Sclerosis registered from 2009 to 2013.

Based on the cutoff duration from the lower limb onset to second region (14 months), all patients were divided into the slowly progressive subtype of lower limb onset Amyotrophic Lateral Sclerosis group and the typical lower limb-onset Amyotrophic Lateral Sclerosis group.

Unsurprisingly the FLS was characterized by slower progression, less and later respiratory dysfunction, and a more benign prognosis than the typical lower limb onset Amyotrophic Lateral Sclerosis.

Patients with FLS exhibited a median diagnostic delay of 25 months, a median duration of 24 months from lower limb onset to second region, a forced vital capacity abnormity rate of 12.5% at the first visit to authors' department, and a median survival time of 80 months, which were significantly different from those of patients with typical lower limb onset Amyotrophic Lateral Sclerosis. The 5-year survival rate of the FLS group was much higher than that of the other group.

Now what all this mean? That if you select patients with a slow progression, you find they have a slow progression, is it high quality science?

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Despite recent studies suggesting a declining incidence and prevalence of dementia on a global scale, epidemiologic results with respect to Alzheimer's disease are lacking due to the methodological limitations inherent to conducting large-scale cohort investigations of this topic.

The aim of the current study was to investigate the incidence and prevalence of Alzheimer's disease in Korea.
The authors conducted a secondary analysis within the National Health Insurance System database, a unique resource that reports medical information for the entire Korean population.

Alzheimer's disease diagnoses as well as evaluations of vascular risks were defined based on International Statistical Classification of Diseases codes along with prescription records.

In this study, the incidence and prevalence of Alzheimer's disease in the Korean population aged 40 years or older showed an overall increase between 2006 and 2015.

Although both older and younger age groups showed an increase in the incidence and prevalence of Alzheimer's disease, the highest increase was observed in older age groups. Which is the inverse of the previous reports.

The average value for the diagnosis of Alzheimer's disease was found to be 69 years.

The incidence of Alzheimer's disease was higher in individuals with underlying vascular risks. However, in recent years, the prevalence of Alzheimer's disease was conversely found to be lower in individuals with hypertension or dyslipidemia.

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While amyotrophic lateral sclerosis is widely recognised as a multi-network disorder with extensive frontotemporal and cerebellar involvement, sensory dysfunction is most of the time denied as "ALS is a motor neuron disease", despite the wide reports of pain by patients and multiple MRI studies telling degeneration in many areas in the brain. This study complements the work in this area, hopefully many progress could be expected when scientists will stop to think of ALS as only "a motor neuron disease".

In a prospective neuroimaging study the authors have systematically evaluated cerebral grey and white matter structures involved in the processing, relaying and mediation of sensory information. Twenty two C9orf72 positive Amyotrophic Lateral Sclerosis patients, 138 C9orf72 negative Amyotrophic Lateral Sclerosis patients and 127 healthy controls were included.

Widespread cortical alterations were observed in C9+ Amyotrophic Lateral Sclerosis including both primary and secondary somatosensory regions. In C9- Amyotrophic Lateral Sclerosis, cortical thickness reductions were observed in the postcentral gyrus.

Thalamic nuclei relaying somatosensory information as well as the medial and lateral geniculate nuclei exhibited volume reductions. Diffusivity indices revealed posterior thalamic radiation pathology and a trend of left medial lemniscus degeneration was also observed in C9- Amyotrophic Lateral Sclerosis.

The authors' radiology data confirm the degeneration of somatosensory, visual and auditory pathways in Amyotrophic Lateral Sclerosis, which is more marked in GGGGCC hexanucleotide repeat expansion carriers.

In contrast to the overwhelming focus on motor system degeneration and frontotemporal dysfunction in recent research studies, authors' findings confirm that sensory circuits are also affected in Amyotrophic Lateral Sclerosis.

The involvement of somatosensory, auditory and visual pathways in Amyotrophic Lateral Sclerosis may have important clinical ramifications which are easily overlooked in the context of unremitting motor decline.

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Advanced therapies, including cell and gene therapies, are in development for Parkinson's disease. In many cases, the goal is to replace the lost dopamine, which is anticipated to improve motor dysfunctions associated with dopamine loss. This publication casts some doubts on this strategy.

For Mariah J Lelos from Cardiff University, it is not clear the extent to which these therapeutic interventions may impact on the wide range of cognitive symptoms that manifest as the disease progresses.

Although the accepted perception is that cognitive symptoms are predominately non-dopaminergic in origin, in this commentary, Lelos argues that several, specific cognitive processes, such as habit formation, working memory and reward processing, have been reported to be dopamine-dependent.

Furthermore, there is evidence of dopaminergic medications modulating these behaviors in Parkinson disease patients. Finally, the potential for cell and gene advanced therapies to influence these symptoms is considered.

Lelos concludes that dopamine replacement through advanced therapies is likely to improve certain dopamine-dependent symptoms, but only sparse clinical data are currently available and the ability to precisely titrate dopamine transmission is likely to be complex.

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Accumulating evidence suggests defective energy metabolism in ALS patients, which contributes to weight loss and a poor prognosis.

Lipid metabolism disorders have been widely reported in patients with ALS, presenting with hypercholesterolemia, hypertriglyceridemia, and other mixed dyslipidemias. Leptin, an adipokine, plays a neuroprotective role in neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Nagel et al. suggested that leptin concentrations were positively correlated with the survival rate in ALS patients, indicating protective effects of leptin in patients with ALS.

Serum leptin concentration is strongly correlated with body weight or BMI, which was also confirmed in this study written by scientists from Chinese Academy of Medical Sciences. And higher body weight and BMI have been found to be associated with a lower risk of ALS and better prognosis in ALS patients.

Adipokines are a group of factors released or secreted by adipose tissue and have many physiological functions, such as fat distribution, energy expenditure, appetite and satiety regulation, insulin secretion and sensitivity, and inflammation.

Previous studies on the biological functions of adiponectin provide some evidence that adiponectin is beneficial in ALS. As one of the most abundant adipokines secreted by adipocytes, adiponectin functions in multiple physiological processes, including insulin sensitization, glucose regulation, lipid metabolism, and anti-inflammatory and antiapoptotic activities.

Fifty-two subjects were recruited between October 2020 and January 2022 among patients newly diagnosed with ALS in the Neurology Department of Peking Union Medical College Hospital. The study also included 24 healthy participants to compare adipokines and other metabolic biomarkers.

When comparing adipokines in patients and controls, the authors, found significant differences in the levels of adiponectin, adipsin, resistin, and visfatin between the two groups.

ALS patients had higher levels of adipokines (adiponectin, adipsin, resistin, and visfatin) and other metabolic biomarkers [C-peptide, glucagon, glucagon-like peptide 1 (GLP-1), gastric inhibitory peptide, and plasminogen activator inhibitor type 1] than controls.

Leptin levels in serum were positively correlated with body mass index, body fat, and visceral fat index.

Adiponectin was positively correlated with the visceral fat index and showed a positive correlation with the ALSFRS-R and a negative correlation with baseline disease progression.

Lower leptin and adiponectin levels were correlated with faster disease progression. After adjusting for confounders, lower adiponectin levels and higher visfatin levels were independently correlated with faster disease progression.

Berberine, an isoquinoline alkaloid, has been shown to increase adiponectin expression, which partly explains its beneficial effects on metabolic disturbances. Mice fed the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), both omega-3 fatty acids, have also shown increased plasma adiponectin. Curcumin, capsaicin, gingerol, and catechins have also been found to increase adiponectin expression.

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The Amyotrophic Lateral Sclerosis diagnostic challenges necessitate more robust diagnostic and prognostic methods. A potential biomarker in this regard is the alterations of ferritin levels in the serum and cerebrospinal fluid of patients compared to controls.

The cerebrospinal fluid and serum ferritin levels were measured in 50 Amyotrophic Lateral Sclerosis cases and 50 control patients with predefined exclusion criteria. The ELISA method was utilized for laboratory measurement and was statistically analyzed using the SPSS.

Heightened serum ferritin levels in cases were not statistically significant, however, cerebrospinal fluid ferritin levels were significantly higher in Amyotrophic Lateral Sclerosis patients.

Serum ferritin levels were significantly negatively correlated with the disease duration and were significantly positively correlated with the disease progression rate.

Heightened cerebrospinal fluid ferritin levels can be used for the diagnosis of Amyotrophic Lateral Sclerosis. The correlation between the serum ferritin levels with the DPR and its correlation with the disease duration suggests potential prognostic utilities.

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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.

Applying machine-learning algorithms to large datasets such as those available in Huntington's disease offers the opportunity to discover hidden patterns, often not discernible to clinical observation.

A computer model of Huntington's disease progression is missing.

Longitudinal data encompassing 2079 assessment measures from four observational studies were integrated and machine-learning methods were applied to develop a probabilistic model of disease progression. The model was validated using a separate Enroll-HD dataset and compared with existing clinical reference assessments and CAG-age product.

Nine disease states were discovered based on 44 motor, cognitive, and functional measures, which correlated with reference assessments.

The validation set included 3158 participants of whom 61.5% had manifest disease. Analysis of transition times showed that "early-disease" states 1 and 2, which occur before motor diagnosis, lasted ~16 years.

Increasing numbers of participants had motor onset during "transition" states 3 to 5, which collectively lasted ~10 years, and the "late-disease" states 6 to 9 also lasted ~10 years. The annual probability of conversion from one of the nine identified disease states to the next ranged from 5% to 27%.

The natural history of Huntington's disease can be described by nine disease states of increasing severity. The ability to derive characteristics of disease states and probabilities for progression through these states will improve trial design and participant selection. © 2021 International Parkinson and Movement Disorder Society.

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