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  1. Article ; Online: Preclinical assessment of a noncooled MR thermometry-based neurosurgical laser therapy system.

    Singh, Hargunbir / Osswald, Christian R / Rossman, Aaron / Knappe, Verena / Schneider, Lonnie / Floyd, Candace L / Rolston, John D

    Journal of neurosurgery

    2024  , Page(s) 1–11

    Abstract: Objective: MRI-guided laser interstitial thermal therapy (MRgLITT) has recently gained interest as an ablative stereotactic procedure for intractable epilepsy, movement disorders, and brain tumors. Conventionally, a LITT system consists of a laser ... ...

    Abstract Objective: MRI-guided laser interstitial thermal therapy (MRgLITT) has recently gained interest as an ablative stereotactic procedure for intractable epilepsy, movement disorders, and brain tumors. Conventionally, a LITT system consists of a laser generator and cooled laser applicator, which is a fiber optic core surrounded by a sheath through which cooled fluid is pumped. However, this footprint can make the system bulky and nonmobile, limit the maximum depth of targeting, and increase the chances of breakdown. Herein, the authors conduct a preclinical assessment of a noncooled MRgLITT system in a porcine model.
    Methods: Three-tesla MRI was used to guide the in vivo placement of noncooled laser applicators in the porcine brain. The study consisted of a survival arm and terminal arm. The laser was activated at a power of 4-7 W for ≤ 180 seconds. Temperature changes were monitored using the MR thermometry software ThermoGuide in the survival arm (n = 5) or both ThermoGuide software and adjacently inserted thermal probes in the terminal arm (n = 3). Thermal damage was determined by the software using the temperature-time relationship of cumulative equivalent minutes at 43°C (CEM43). Temperatures calculated by the software were compared with those recorded by the temperature probes. The dimensions of thermal damage thresholds (TDTs; 2-9, 10-59, 60-239, ≥ 240 CEM43 isolines) given by MR thermometry were compared with the dimensions of irreversible damage on histopathological analysis.
    Results: There was a strong correlation between temperature recordings by ThermoGuide and those by thermal probes at both 4 mm (r = 0.96) and 8 mm (r = 0.80), with a mean absolute error of 0.76°C ± 2.13°C and 0.17°C ± 1.65°C at 4 and 8 mm, respectively. The area of 2-9 CEM43 was larger than the area of irreversible damage seen on histopathological analysis. The dimensions of the 10 and 60 CEM43 correlated well with dimensions of the lesion on histopathological analysis. A well-defined border (≤ 1 mm) was observed between the area of irreversible damage and healthy brain tissue.
    Conclusions: This preclinical assessment showed that the noncooled LITT system was able to precisely reach the target and create well-defined lesions within a margin of safety, without any adverse effects. MR thermometry software provided an accurate near-real-time temperature of the brain tissue, and dimensions of the lesion as visualized by the software correlated well with histopathological findings. Further studies to test the system's efficacy and safety in human subjects are in progress.
    Language English
    Publishing date 2024-03-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3089-2
    ISSN 1933-0693 ; 0022-3085
    ISSN (online) 1933-0693
    ISSN 0022-3085
    DOI 10.3171/2023.12.JNS232154
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The human anti-ganglioside GM1 autoantibody response following traumatic and surgical central nervous system insults.

    Schneider, Lonnie / Rezaeezade-Roukerd, Maryam / Faulkner, Jenna / Reichert, Ethan / Abou-Al-Shaar, Hussam / Flis, Alexandra / Rubiano, Andres M / Hawryluk, Gregory W J

    Neuroscience research

    2022  Volume 181, Page(s) 105–114

    Abstract: Predictors of the central nervous system (CNS) directed autoantibody response after acute CNS injury are poorly understood. We analyzed titers of IgG and IgM autoantibodies to ganglioside GM1 in serial serum specimens collected from human patients ... ...

    Abstract Predictors of the central nervous system (CNS) directed autoantibody response after acute CNS injury are poorly understood. We analyzed titers of IgG and IgM autoantibodies to ganglioside GM1 in serial serum specimens collected from human patients following acute spinal cord injury (SCI), traumatic brain injury (TBI) and brain tumor resection. We also assessed putative predictors of the autoantibody titers. We enrolled 19 patients with acute SCI, 14 patients with acute severe TBI, and 19 patients undergoing brain tumor resection. We also enrolled 25 control subjects. Some SCI, TBI and tumor patients exhibited elevated IgG titers as compared with control values; some SCI and TBI patients exhibited an acute peak in IgG titers, most commonly 14 days after insult. Some clinical and radiographic measures of injury severity correlated with IgG titer elevation in SCI and TBI patients but not tumor patients. Our study demonstrates that diverse CNS insults are followed by increased IgG autoimmune antibody titers to the CNS antigen ganglioside GM1, however the response inherent to each insult type is unique. IgG autoimmune antibody titers to GM1 merit further study as a biomarker of traumatic injury severity that can be measured in delayed fashion after CNS insult. These human data help to inform which patients with CNS insults are at risk for CNS-directed autoimmunity as well as the time course of the response.
    MeSH term(s) Autoantibodies ; Brain Injuries, Traumatic ; Brain Neoplasms ; Central Nervous System ; G(M1) Ganglioside ; Humans ; Immunoglobulin G ; Spinal Cord Injuries
    Chemical Substances Autoantibodies ; Immunoglobulin G ; G(M1) Ganglioside (37758-47-7)
    Language English
    Publishing date 2022-04-08
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 605842-5
    ISSN 1872-8111 ; 0168-0102 ; 0921-8696
    ISSN (online) 1872-8111
    ISSN 0168-0102 ; 0921-8696
    DOI 10.1016/j.neures.2022.03.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: CNS inflammation and neurodegeneration: sequelae of peripheral inoculation with spinal cord tissue in rat.

    Schneider, Lonnie / Reichert, Ethan / Faulkner, Jenna / Reichert, Brielle / Sonnen, Joshua / Hawryluk, Gregory W J

    Journal of neurosurgery

    2019  Volume 132, Issue 3, Page(s) 933–944

    Abstract: Objective: Recent research demonstrates that victims of spinal cord injury (SCI) are at increased risk for dementia and that encephalitis can occur as a consequence of isolated SCI. We theorize that autoimmunity to the central nervous system (CNS) could ...

    Abstract Objective: Recent research demonstrates that victims of spinal cord injury (SCI) are at increased risk for dementia and that encephalitis can occur as a consequence of isolated SCI. We theorize that autoimmunity to the central nervous system (CNS) could explain these phenomena and undertook this study to determine whether peripheral inoculation with spinal cord homogenate on 1 or 2 occasions is associated with CNS-directed autoimmunity and neurodegeneration in a rat model.
    Methods: Rats were subcutaneously inoculated with saline or 75 mg of allogeneic spinal cord tissue on 1 or 2 occasions. Animals underwent Morris Water Maze testing, and serial serum samples were collected. Animals were sacrificed 8 weeks following the first inoculation. Autoantibody titers to myelin antigens MAG and GM1 were measured in serum. Immunohistochemistry was used to identify autoantibodies targeting NeuN-labeled neurons and CC1-labeled oligodendrocytes. Quantitative real-time polymerase chain reaction (qPCR) and western blotting were performed for pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 and the cell death marker caspase 3 as well as the neurodegenerative proteins tau and β-amyloid in both brain and spinal cord. Fluoro-Jade B was used to stain degenerating neurons, facilitating counting.
    Results: Animals inoculated with spinal cord homogenate exhibited increased titers of autoantibodies to MAG and GM1 and autoantibodies binding to neurons and oligodendrocytes. Double-inoculated animals demonstrated a significant increase in the expression of pro-inflammatory cytokines in the brain (TNF-α, p = 0.016; IL-6, p = 0.009) as well as the spinal cord (TNF-α, p = 0.024; IL-6, p = 0.002). The number of degenerating neurons was significantly increased in the brain and spinal cord of inoculated animals (p < 0.0001 and p = 0.028, respectively). Elevated expression of tau and β-amyloid was seen in brain of double-inoculated animals (p = 0.003 and p = 0.009, respectively). Inflammatory marker expression in the brain was positively correlated with anti-myelin autoimmune antibody titers and with tau expression in the brain. Inoculated animals showed impaired memory function in Morris Water Maze testing (p = 0.043).
    Conclusions: The results of these experiments demonstrate that peripheral exposure to spinal cord antigens is associated with CNS-directed autoimmunity and inflammation in the brain and spinal cord as well as degeneration of CNS cells, memory impairment, and production of neurodegenerative proteins particularly when this exposure is repeated. These data support CNS autoimmunity as a candidate mechanism for the dementia that can follow SCI and perhaps other posttraumatic dementias such as chronic traumatic encephalopathy.
    Language English
    Publishing date 2019-02-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3089-2
    ISSN 1933-0693 ; 0022-3085
    ISSN (online) 1933-0693
    ISSN 0022-3085
    DOI 10.3171/2018.10.JNS181517
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Cancer risk with topical calcineurin inhibitors, pimecrolimus and tacrolimus, for atopic dermatitis: a systematic review and meta-analysis.

    Devasenapathy, Niveditha / Chu, Alexandro / Wong, Melanie / Srivastava, Archita / Ceccacci, Renata / Lin, Clement / MacDonald, Margaret / Wen, Aaron / Steen, Jeremy / Levine, Mitchell / Pyne, Lonnie / Schneider, Lynda / Chu, Derek K

    The Lancet. Child & adolescent health

    2022  Volume 7, Issue 1, Page(s) 13–25

    Abstract: Background: Atopic dermatitis is a prevalent condition in children and can be effectively managed with medications such as topical calcineurin inhibitors (pimecrolimus or tacrolimus). A key unresolved safety concern is whether use of topical calcineurin ...

    Abstract Background: Atopic dermatitis is a prevalent condition in children and can be effectively managed with medications such as topical calcineurin inhibitors (pimecrolimus or tacrolimus). A key unresolved safety concern is whether use of topical calcineurin inhibitors is associated with cancer. We systematically reviewed the risk of cancer in patients with atopic dermatitis exposed to topical calcineurin inhibitors.
    Methods: As part of the 2022 American Academy of Allergy, Asthma and Immunology and American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters atopic dermatitis guidelines, we searched MEDLINE, Embase, the Latin American and Caribbean Health Sciences Literature database, the Índice Bibliográfico Espanhol de Ciências da Saúde database, the Global Resource of Eczema Trials database, WHO's International Clinical Trials Registry Platform, the US Food and Drug Administration database, the European Medicines Agency database, company registers, and relevant citations from inception to June 6, 2022. We included randomised controlled trials and comparative and non-comparative non-randomised studies in any language addressing cancer risk in patients with atopic dermatitis using topical calcineurin inhibitors. We excluded split-body studies and studies with less than 3 weeks of follow-up. Paired reviewers independently screened records, extracted data, and assessed risk of bias in duplicate. We used Bayesian models to estimate the probability for cancer due to topical calcineurin inhibitor exposure and the GRADE approach to determine the certainty of the evidence. Patients, advocacy groups, and care providers set a priori thresholds of important effects. This study is registered with Open Science Framework, https://osf.io/v4bfc.
    Findings: We identified and analysed 110 unique studies (52 randomised controlled trials and 69 non-randomised studies [11 were non-randomised study extensions of randomised controlled trials]) including 3·4 million patients followed up for a mean of 11 months (range 0·7-120). The absolute risk of any cancer with topical calcineurin inhibitor exposure was not different from controls (absolute risk 4·70 per 1000 with topical calcineurin inhibitors vs 4·56 per 1000 without; odds ratio 1·03 [95% credible interval 0·94-1·11]; moderate certainty). For all age groups and using data from observational studies and randomised controlled trials, the use of pimecrolimus (OR 1·05 [95% credible interval 0·94-1·15]) or tacrolimus (0·99 [0·89-1·09]) is likely to have had little to no association with cancer compared with no topical calcineurin inhibitor exposure. For pimecrolimus versus tacrolimus, the finding was similar (0·95 [95% credible interval 0·83-1·07]). Findings were similar in infants, children, and adults, and robust to trial sequential, subgroup, and sensitivity analyses.
    Interpretation: Among individuals with atopic dermatitis, moderate-certainty evidence shows that topical calcineurin inhibitors do not increase the risk of cancer. These findings support the safe use of topical calcineurin inhibitors in the optimal treatment of patients with atopic dermatitis.
    Funding: American Academy of Allergy, Asthma and Immunology and American College of Allergy, Asthma and Immunology via the Joint Task Force on Practice Parameters.
    MeSH term(s) Adult ; Child ; Humans ; Infant ; Asthma ; Bayes Theorem ; Calcineurin Inhibitors/adverse effects ; Dermatitis, Atopic/drug therapy ; Dermatitis, Atopic/epidemiology ; Hypersensitivity ; Neoplasms/drug therapy ; Tacrolimus/adverse effects ; Controlled Clinical Trials as Topic
    Chemical Substances Calcineurin Inhibitors ; pimecrolimus (7KYV510875) ; Tacrolimus (WM0HAQ4WNM)
    Language English
    Publishing date 2022-11-10
    Publishing country England
    Document type Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Systematic Review
    ISSN 2352-4650
    ISSN (online) 2352-4650
    DOI 10.1016/S2352-4642(22)00283-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Lysosomal function in macromolecular homeostasis and bioenergetics in Parkinson's disease

    Zhang Jianhua / Schneider Lonnie

    Molecular Neurodegeneration, Vol 5, Iss 1, p

    2010  Volume 14

    Abstract: Abstract The pathological changes occurring in Parkinson's and several other neurodegenerative diseases are complex and poorly understood, but all clearly involve protein aggregation. Also frequently appearing in neurodegeneration is mitochondrial ... ...

    Abstract Abstract The pathological changes occurring in Parkinson's and several other neurodegenerative diseases are complex and poorly understood, but all clearly involve protein aggregation. Also frequently appearing in neurodegeneration is mitochondrial dysfunction which may precede, coincide or follow protein aggregation. These observations led to the concept that protein aggregation and mitochondrial dysfunction either arise from the same etiological factors or are interactive. Understanding the mechanisms and regulation of processes that lead to protein aggregation or mitochondrial dysfunction may therefore contribute to the design of better therapeutics. Clearance of protein aggregates and dysfunctional organelles is dependent on macroautophagy which is the process through which aged or damaged proteins and organelles are first degraded by the lysosome and then recycled. The macroautophagy-lysosomal pathway is essential for maintaining protein and energy homeostasis. Not surprisingly, failure of the lysosomal system has been implicated in diseases that have features of protein aggregation and mitochondrial dysfunction. This review summarizes 3 major topics: 1) the current understanding of Parkinson's disease pathogenesis in terms of accumulation of damaged proteins and reduction of cellular bioenergetics; 2) evolving insights into lysosomal function and biogenesis and the accumulating evidence that lysosomal dysfunction may cause or exacerbate Parkinsonian pathology and finally 3) the possibility that enhancing lysosomal function may provide a disease modifying therapy.
    Keywords Neurology. Diseases of the nervous system ; RC346-429 ; Neurosciences. Biological psychiatry. Neuropsychiatry ; RC321-571 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Neurology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Subject code 612
    Language English
    Publishing date 2010-04-01T00:00:00Z
    Publisher BioMed Central
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Lysosomal function in macromolecular homeostasis and bioenergetics in Parkinson's disease.

    Schneider, Lonnie / Zhang, Jianhua

    Molecular neurodegeneration

    2010  Volume 5, Page(s) 14

    Abstract: The pathological changes occurring in Parkinson's and several other neurodegenerative diseases are complex and poorly understood, but all clearly involve protein aggregation. Also frequently appearing in neurodegeneration is mitochondrial dysfunction ... ...

    Abstract The pathological changes occurring in Parkinson's and several other neurodegenerative diseases are complex and poorly understood, but all clearly involve protein aggregation. Also frequently appearing in neurodegeneration is mitochondrial dysfunction which may precede, coincide or follow protein aggregation. These observations led to the concept that protein aggregation and mitochondrial dysfunction either arise from the same etiological factors or are interactive. Understanding the mechanisms and regulation of processes that lead to protein aggregation or mitochondrial dysfunction may therefore contribute to the design of better therapeutics. Clearance of protein aggregates and dysfunctional organelles is dependent on macroautophagy which is the process through which aged or damaged proteins and organelles are first degraded by the lysosome and then recycled. The macroautophagy-lysosomal pathway is essential for maintaining protein and energy homeostasis. Not surprisingly, failure of the lysosomal system has been implicated in diseases that have features of protein aggregation and mitochondrial dysfunction. This review summarizes 3 major topics: 1) the current understanding of Parkinson's disease pathogenesis in terms of accumulation of damaged proteins and reduction of cellular bioenergetics; 2) evolving insights into lysosomal function and biogenesis and the accumulating evidence that lysosomal dysfunction may cause or exacerbate Parkinsonian pathology and finally 3) the possibility that enhancing lysosomal function may provide a disease modifying therapy.
    Language English
    Publishing date 2010-04-13
    Publishing country England
    Document type Journal Article
    ISSN 1750-1326
    ISSN (online) 1750-1326
    DOI 10.1186/1750-1326-5-14
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Reduction of mutant huntingtin accumulation and toxicity by lysosomal cathepsins D and B in neurons

    Ouyang Xiaosen / Liang Qiuli / Schneider Lonnie / Zhang Jianhua

    Molecular Neurodegeneration, Vol 6, Iss 1, p

    2011  Volume 37

    Abstract: Abstract Background Huntington's disease is caused by aggregation of mutant huntingtin (mHtt) protein containing more than a 36 polyQ repeat. Upregulation of macroautophagy was suggested as a neuroprotective strategy to degrade mutant huntingtin. However, ...

    Abstract Abstract Background Huntington's disease is caused by aggregation of mutant huntingtin (mHtt) protein containing more than a 36 polyQ repeat. Upregulation of macroautophagy was suggested as a neuroprotective strategy to degrade mutant huntingtin. However, macroautophagy initiation has been shown to be highly efficient in neurons whereas lysosomal activities are rate limiting. The role of the lysosomal and other proteases in Huntington is not clear. Some studies suggest that certain protease activities may contribute to toxicity whereas others are consistent with protection. These discrepancies may be due to a number of mechanisms including distinct effects of the specific intermediate digestion products of mutant huntingtin generated by different proteases. These observations suggested a critical need to investigate the consequence of upregulation of individual lysosomal enzyme in mutant huntingtin accumulation and toxicity. Results In this study, we used molecular approaches to enhance lysosomal protease activities and examined their effects on mutant huntingtin level and toxicity. We found that enhanced expression of lysosomal cathepsins D and B resulted in their increased enzymatic activities and reduced both full-length and fragmented huntingtin in transfected HEK cells. Furthermore, enhanced expression of cathepsin D or B protected against mutant huntingtin toxicity in primary neurons, and their neuroprotection is dependent on macroautophagy. Conclusions These observations demonstrate a neuroprotective effect of enhancing lysosomal cathepsins in reducing mutant huntingtin level and toxicity in transfected cells. They highlight the potential importance of neuroprotection mediated by cathepsin D or B through macroautophagy.
    Keywords huntingtin ; lysosome ; cathepsin ; autophagy ; Neurology. Diseases of the nervous system ; RC346-429 ; Neurosciences. Biological psychiatry. Neuropsychiatry ; RC321-571 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Neurology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Subject code 572
    Language English
    Publishing date 2011-06-01T00:00:00Z
    Publisher BioMed Central
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Application of the Rat Grimace Scale as a Marker of Supraspinal Pain Sensation after Cervical Spinal Cord Injury.

    Schneider, Lonnie E / Henley, Kathryn Y / Turner, Omari A / Pat, Betty / Niedzielko, Tracy L / Floyd, Candace L

    Journal of neurotrauma

    2017  Volume 34, Issue 21, Page(s) 2982–2993

    Abstract: Experimental models of neuropathic pain (NP) typically rely on withdrawal responses to assess the presence of pain. Reflexive withdrawal responses to a stimulus are used to evaluate evoked pain and, as such, do not include the assessment of spontaneous ... ...

    Abstract Experimental models of neuropathic pain (NP) typically rely on withdrawal responses to assess the presence of pain. Reflexive withdrawal responses to a stimulus are used to evaluate evoked pain and, as such, do not include the assessment of spontaneous NP nor evaluation of the affective and emotional consequences of pain in animal models. Additionally, withdrawal responses can be mediated by spinal cord reflexes and may not accurately indicate supraspinal pain sensation. This is especially true in models of traumatic spinal cord injury (SCI), wherein spastic syndrome, a motor disorder characterized by exaggeration of the stretch reflex that is secondary to hyperexcitability of the spinal reflex, can cause paroxysmal withdrawals not associated with NP sensation. Consequently, the aim of this study was to utilize an assessment of supraspinal pain sensation, the Rat Grimace Scale (RGS), to measure both spontaneous and evoked NP after a contusion SCI at cervical level 5 in adult male rats. Spontaneous and evoked pain were assessed using the RGS to score facial action units before and after the application of a stimulus, respectively. Rodents exhibited significantly higher RGS scores at week 5 post-injury as compared to baseline and laminectomy controls before the application of the stimulus, suggesting the presence of spontaneous NP. Additionally, there was a significant increase in RGS scores after the application of the acetone. These data suggest that the RGS can be used to assess spontaneous NP and determine the presence of evoked supraspinal pain sensation after experimental cervical SCI.
    MeSH term(s) Animals ; Cervical Vertebrae ; Facial Expression ; Male ; Neuralgia/etiology ; Pain Measurement/methods ; Rats ; Rats, Sprague-Dawley ; Spinal Cord Injuries/complications
    Language English
    Publishing date 2017-06-26
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
    ZDB-ID 645092-1
    ISSN 1557-9042 ; 0897-7151
    ISSN (online) 1557-9042
    ISSN 0897-7151
    DOI 10.1089/neu.2016.4665
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Reduction of mutant huntingtin accumulation and toxicity by lysosomal cathepsins D and B in neurons.

    Liang, Qiuli / Ouyang, Xiaosen / Schneider, Lonnie / Zhang, Jianhua

    Molecular neurodegeneration

    2011  Volume 6, Page(s) 37

    Abstract: Background: Huntington's disease is caused by aggregation of mutant huntingtin (mHtt) protein containing more than a 36 polyQ repeat. Upregulation of macroautophagy was suggested as a neuroprotective strategy to degrade mutant huntingtin. However, ... ...

    Abstract Background: Huntington's disease is caused by aggregation of mutant huntingtin (mHtt) protein containing more than a 36 polyQ repeat. Upregulation of macroautophagy was suggested as a neuroprotective strategy to degrade mutant huntingtin. However, macroautophagy initiation has been shown to be highly efficient in neurons whereas lysosomal activities are rate limiting. The role of the lysosomal and other proteases in Huntington is not clear. Some studies suggest that certain protease activities may contribute to toxicity whereas others are consistent with protection. These discrepancies may be due to a number of mechanisms including distinct effects of the specific intermediate digestion products of mutant huntingtin generated by different proteases. These observations suggested a critical need to investigate the consequence of upregulation of individual lysosomal enzyme in mutant huntingtin accumulation and toxicity.
    Results: In this study, we used molecular approaches to enhance lysosomal protease activities and examined their effects on mutant huntingtin level and toxicity. We found that enhanced expression of lysosomal cathepsins D and B resulted in their increased enzymatic activities and reduced both full-length and fragmented huntingtin in transfected HEK cells. Furthermore, enhanced expression of cathepsin D or B protected against mutant huntingtin toxicity in primary neurons, and their neuroprotection is dependent on macroautophagy.
    Conclusions: These observations demonstrate a neuroprotective effect of enhancing lysosomal cathepsins in reducing mutant huntingtin level and toxicity in transfected cells. They highlight the potential importance of neuroprotection mediated by cathepsin D or B through macroautophagy.
    Language English
    Publishing date 2011-06-01
    Publishing country England
    Document type Journal Article
    ISSN 1750-1326
    ISSN (online) 1750-1326
    DOI 10.1186/1750-1326-6-37
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Bioinformatics curriculum guidelines

    Lonnie Welch / Fran Lewitter / Russell Schwartz / Cath Brooksbank / Predrag Radivojac / Bruno Gaeta / Maria Victoria Schneider

    PLoS Computational Biology, Vol 10, Iss 3, p e

    toward a definition of core competencies.

    2014  Volume 1003496

    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2014-03-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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