Skin In Amyotrophic Lateral Sclerosis Research Articles

Increased progranulin in the skin of amyotrophic lateral sclerosis: An immunohistochemical study

Background and objective: It has been demonstrated that progranulin (PGRN) is a neurotrophic factor that enhances neuronal survival and axonal growth. Several lines of evidence have indicated that PGRN plays a role in the pathomechanism of amyotrophic lateral sclerosis (ALS). So far studies of ALS skin have shown unique pathological and biochemical abnormalities. The lack of bedsore formation in ALS patients is considered characteristic. However, there has been no study of PGRN in ALS skin.

Decreased amount of collagen in the skin of amyotrophic lateral sclerosis in the Kii Peninsula of Japan

Decreased amount of collagen in the skin of amyotrophic lateral sclerosis in the Kii Peninsula of Japan

Expression of hepatocyte growth factor in the skin of amyotrophic lateral sclerosis

Hepatocyte growth factor (HGF) is one of the most potent survival-promoting factors for motor neurons. Overexpression of neuronal HGF has been shown to result in the attenuation of neuronal cell death and progression of disease in a familial amyotrophic lateral sclerosis (ALS) transgenic mouse model. HGF might be beneficial for motor neuron survival and is a good candidate agent for the treatment of ALS. So far, studies of the skin of ALS have shown unique pathological and biochemical abnormalities. However, there has been no study of HGF in ALS skin. We made a quantitative immunohistochemical study of the expression of HGF in the skin from 19 patients with sporadic ALS and 16 controls. Hepatocyte growth factor immunoreactivity was positive in the epidermis, some dermal blood vessels, and glands in patients with ALS. These findings became more conspicuous as ALS progressed. The optical density for HGF immunoreactivity of the nucleus and the cytoplasm in the epidermis in ALS was significantly higher (P < 0.001 and P < 0.001) than in controls. There was a significant positive relation (r = 0.53, P < 0.02 and r = 0.73, P < 0.001) between HGF immunoreactivity and duration of illness in the nucleus and the cytoplasm in the epidermis in patients with ALS. These findings suggest that changes in HGF in ALS skin are related to the disease process and that metabolic alterations of HGF may take place in the skin of patients with ALS.

Increased progranulin in the skin of amyotrophic lateral sclerosis: An immunohistochemical study

It has been demonstrated that progranulin (PGRN) is a neurotrophic factor that enhances neuronal survival and axonal growth. Several lines of evidence have indicated that PGRN plays a role in the pathomechanism of amyotrophic lateral sclerosis (ALS). However, there has no study of PGRN in ALS skin. We made a quantitative immunohistochemical study of the expression of PGRN in the skin from 18 patients with sporadic ALS and 13 control subjects. Immunohistochemistry for PGRN demonstrated cytoplasmic activity in the epidermis and in some blood vessels and glands. Numerous PGRN-positive (PGRN+) cells were observed in the epidermis in ALS patients, which became more marked as ALS progressed. PGRN immunoreactivity of PGRN + cells was markedly positive in the epidermis in ALS patients. The proportion of PGRN + cells in the epidermis in ALS patients was significantly higher (p < 0.001) than in controls. There was a significant positive relationship (r = 0.83, p < 0.001) between the proportion and duration of illness in ALS patients. These data suggest that changes of PGRN in ALS skin are related to the disease process and that metabolic alteration of PGRN may take place in the skin of patients with ALS.

Increased expression of TDP-43 in the skin of amyotrophic lateral sclerosis

Transactivation-responsive DNA-binding protein-43 (TDP-43) was identified as a major component of the ubiquitin-positive inclusions in sporadic amyotrophic lateral sclerosis (ALS). However, there has been no study of TDP-43 in ALS skin. The present study investigates TDP-43 in ALS skin. We made a quantitative immunohistochemical study of the expression of TDP-43 in the skin from 15 patients with ALS and 15 control subjects. The proportion of TDP-43-positive (TDP-43+) cells in the epidermis in ALS patients was significantly higher (P < 0.001) than in controls. There was a significant positive relationship (r = 0.62, P < 0.02) between the proportion and duration of illness in ALS patients. The optical density of TDP-43+ cells in the epidermis in ALS patients is markedly stronger (P < 0.001) than in controls. There was a significant positive relation (r = 0.72, P < 0.01) between the immunoreactivity and duration of illness in ALS patients. These data suggest that changes of TDP-43 in ALS skin are likely to be related to the disease process and that metabolic alterations of TDP-43 may take place in the skin of patients with ALS.

FP57-FR-06 Increased neurotrophin-3 of skin in amyotrophic lateral sclerosis: an immunohistochemical study

FP57-FR-06 Increased neurotrophin-3 of skin in amyotrophic lateral sclerosis: an immunohistochemical study

Immunohistochemical studies of vascular endothelial growth factor in skin of patients with amyotrophic lateral sclerosis

Vascular endothelial growth factor (VEGF) is a disulfide-linked dimeric glycoprotein that enhances vascular permeability, induces chemotaxis and activation of monocytes/macrophages, and promotes growth of vascular endothelial cells. Furthermore, VEGF is a multifunctional cytokine, which influences neural cells directly, enhancing neuronal survival, axonal outgrowth, and Schwann cell proliferation. So far studies of the skin of amyotrophic lateral sclerosis (ALS) have shown unique pathological and biochemical abnormalities in collagen, elastic fibers, and the ground substance. However, the expression of VEGF in ALS skin has not previously been studied. We made a quantitative immunohistochemical study of the expression of VEGF in the skin from 15 patients with ALS and 15 control subjects. VEGF immunoreactivity was markedly positive in the epidermis and moderately positive in some dermal blood vessels and glands in ALS patients. These findings became more conspicuous as ALS progressed. The optical densities for VEGF immunoreactivity of the epidermis in ALS patients were significantly higher ( p < 0.001) than in control subjects. In addition, there was an appreciable positive correlation ( r = 0.85, p < 0.001) in ALS patients between the densities for VEGF immunoreactivity and duration of illness, but there was no such correlation in control subjects. These data suggest that changes of VEGF in ALS skin are likely to be related to the disease process and that metabolic alterations of VEGF may take place in the skin of patients with ALS.

Are there specific histologic abnormalities of skin in amyotrophic lateral sclerosis?

Acta Neurologica ScandinavicaVolume 81, Issue 6 p. 555-556 Are there specific histologic abnormalities of skin in amyotrophic lateral sclerosis? Giorgio Mapelli, Giorgio Mapelli Clinical Neurology Institute Ferrara ItalySearch for more papers by this author Giorgio Mapelli, Giorgio Mapelli Clinical Neurology Institute Ferrara ItalySearch for more papers by this author First published: June 1990 https://doi.org/10.1111/j.1600-0404.1990.tb01019.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume81, Issue6June 1990Pages 555-556 RelatedInformation

Decreased galectin-1 immunoreactivity of the skin in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease involving motor neurons. In addition to motor neuron signs and symptoms, a lack of bedsores has been considered a feature of ALS. Recently, we revealed that galectin-1 is a component of the axonal spheroid, which is an early pathological change of the spinal cord in ALS. To investigate whether galectin-1 is associated with skin changes in ALS, we performed an immunohistochemical investigation using anti-galectin-1 antibodies. The present study revealed that galectin-1 immunoreactivity is reduced in the skin of patients with ALS, suggesting that cutaneous galectin-1 is involved in the pathological process of ALS.

Increased interleukin-6 of skin and serum in amyotrophic lateral sclerosis

Studies of skin in amyotrophic lateral sclerosis (ALS) have demonstrated morphological and biochemical alterations. Interleukin-6 (IL-6) has been suggested to have a trophic effect in nerve cells and to have a direct pathogenic role in neurodegenerative central nervous system (CNS) disorders. However, little is known concerning IL-6 in ALS patients. We examined IL-6 immunoreactivity of biopsy specimens of skin and measured serum IL-6 levels from 11 ALS patients and 11 diseased control subjects. IL-6 immunoreactivity was markedly positive in the epidermis and dermal blood vessels and glands and was moderately positive in the reticular dermis in all ALS patients. These optical densities for IL-6 immunoreactivity in ALS patients were significantly higher than in control subjects, and were significantly increased with duration of illness. Serum IL-6 levels were detected in 8 (73%) of 11 ALS patients compared with only 1 (9%) of 11 diseased control subjects. Serum IL-6 levels were significantly correlated with duration of illness in ALS patients and immunoreactivity of IL-6 of the epidermis. These data suggest that the increased levels of serum IL-6 may reflect an increased IL-6 immunoreactivity of skin in ALS patients.

Increased expression of insulin-like growth factor I in skin in amyotrophic lateral sclerosis

OBJECTIVESInsulin-like growth factor I (IGF-I) has potent effects on motor neuron survival and is being studied as a possible therapeutic agent for ALS. However, little is known concerning IGF-I in...

Increased cystatin C immunoreactivity in the skin in amyotrophic lateral sclerosis.

Several abnormalities of skin have been described in patients with amyotrophic lateral sclerosis (ALS). Bunina bodies, which are small eosinophilic intraneuronal inclusions in the remaining lower motor neurons in ALS, are the only pathologically specific hallmark of ALS. It has been demonstrated that Bunina bodies were positive for anti-cystatin C serum. However, cystatin C in the skin of ALS has not been investigated. We studied cystatin C immunoreactivity of skin in ALS patients, and the results were compared with those of control subjects. The epidermis of ALS was immunohistochemically strongly positive for cystatin C as compared with that of controls. The optical density of cystatin C immunostaining reactivity in ALS patients was significantly higher than in controls, and was significantly increased with duration of illness. These data suggest that a metabolic alteration of cystatin C may take place in the skin of ALS and the increased cystatin C in skin is likely to be related to the disease process in ALS.

Increased Expression of Laminin 1 in the Skin of Amyotrophic Lateral Sclerosis

Abnormalities of collagen and glycosaminoglycans of skin have been reported in patients with amyotrophic lateral sclerosis (ALS). However, little is known concerning laminin in ALS. The aim of this study is to evaluate laminin 1 immunohistochemistry of skin in ALS patients. We studied laminin 1 immunoreactivity of skin from 17 patients with ALS, 17 patients with other neurological or muscular diseases (control group A) and 10 patients without neurological or muscular disorders (control group B). The dermis, the epithelial basement membrane of the epidermal layer and the basement membrane of skin appendages and blood vessels of skin in ALS patients were significantly higher than in control groups A and B, and showed a significant positive correlation with the duration of illness in the optical density for laminin 1 immunoreactivity. In addition, there was an appreciable positive relationship in the laminin 1 immunoreactivity between the dermis and the basement membrane in ALS patients. These data suggest that alterations of laminin 1 in the skin of ALS patients could be related to the pathogenesis of ALS and may contribute to changes in the mechanical properties of the skin, resulting in the absence of bedsores in ALS patients.

The skin in amyotrophic lateral sclerosis

It has been repeatedly noted, but never as yet fully explained, that patients with ALS do not develop bedsores even at the terminal stage. Furthermore, the skin of ALS patients feels supple, like tanned leather, and loses elasticity. When the skin is stretched, it returns only sluggishly to its original position. We termed this property of skin 'delayed return phenomenon (DRP)'; it is usually seen more than 2 1/2 years after the onset of symptoms. Though it is thought that phenomena such as DRP and the absence of bedsores are characteristic of this disease, little attention has been paid to these unique features in ALS patients. In this review we summarize recent developments in research on skin from ALS patients, which may give insight into the possible mechanisms and pathogenesis underlying this disorder.

Expression of leukaemia inhibitory factor in skin of patients with amyotrophic lateral sclerosis

One of the remarkable features of patients with amyotrophic lateral sclerosis (ALS) is absence of bedsores. 1 Furukawa T Toyokura Y Amyotrophic lateral sclerosis and bedsores. Lancet. 1976; i: 862 Abstract Scopus (56) Google Scholar Our previous reports have shown morphological and biochemical alterations in the skin of patients with ALS. 2 Ono S Nagao K Yamauchi M Amorphous material of skin in amyotrophic lateral sclerosis: a morphologic and biochemical study. Neurology. 1994; 44: 537-540 Crossref PubMed Google Scholar , 3 Ono S Imai T Shimizu N Nakagawa H Hu J Ciliary neutrophic fact or in skin biopsies of patients with amyotrophic lateral sclerosis. Lancet. 1998; 352: 958-959 PubMed Google Scholar Leukaemia inhibitory factor (LIF) belongs to a group of cytokines including CNTF, IL-6, CT-1, OM, and IL-11. All the group members have different biological effects, but use gp130 signal-transducing subunit as common receptor. LIF is located on the long arm of chromosome 22, adjacent to the sporadic ALS-related NF-H gene. 4 Meyer MA Potter NT Sporadic ALS and chromosome 22: evidence for a possible neurofilament gene defect. Muscle Nerve. 1995; 18: 536-539 Crossref PubMed Scopus (13) Google Scholar LIF affects survival and maintenance of both motor and sensory neurons, and promotes the differentiation of neuronal and astrocytic precursors within the developing spinal cord. LIF also acts as a myogenic growth factor, stimulating muscle regeneration. LIF is significantly upregulated in spinal cord when neurons are damaged by BOAA toxin, an excitatory aminoacid associated with a form of ALS. LIF is now under clinical investigation as a treatment for ALS. 5 Kurek JB Radford AJ Crump DE et al. (AM424) a promising growth factor for the treatment of ALS. J Neurol Sci. 1998; 160: S106-S113 Summary Full Text Full Text PDF PubMed Scopus (47) Google Scholar However, little is known about whether expression of LIF is altered in the skin of patients with ALS.

Amorphous material of the skin in amyotrophic lateral sclerosis

We performed morphologic studies on skin from seven patients with ALS and seven control subjects. By light microscopy, the wide spaces that separated collagen bundles reacted strongly with colloidal iron and alcian blue in ALS patients. Electron microscopy revealed markedly increased amorphous material that was positive for ruthenium red in the ground substance. These findings were not present in controls. Quantitative amino acid analysis showed that the amount of total amino acids (nmoles per mg dry weight) was significantly decreased (p < 0.01) in ALS patients compared with that of controls, and there was a significant negative correlation between skin amino acid content and duration of illness in ALS patients (r = -0.83, p < 0.001). These morphologic findings and biochemical data indicate that the amorphous material, which is markedly increased in ALS skin, includes glycosaminoglycans.

Glutamate and aspartate are decreased in the skin in amyotrophic lateral sclerosis.

We measured the levels of amino acids in biopsied skin from eight patients with amyotrophic lateral sclerosis (ALS) and seven controls. The most conspicuous changes in ALS patients were as follows. First, the contents of the acidic amino acids glutamate and aspartate were significantly decreased in ALS, and were negatively and significantly associated with the duration of illness. Second, the levels of the collagen-associated amino acids hydroxyproline, proline, glycine, alanine, and hydroxylysine were significantly decreased in ALS, and correlated inversely with the duration of illness. These results suggest that there are abnormalities of acidic amino acids and collagen-associated amino acids in the skin of patients with ALS. These changes may underlie the pathogenesis of ALS.