Genetics of the neuronal ceroid lipofuscinoses

Peltonen, Leena; Savukoski, Minna; Vesa, Jouni

doi:10.1016/s0959-437x(00)00086-1

Cited by 28 publications

(12 citation statements)

References 60 publications

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“…Similar hypothesis has been proposed for a group of genetic neurodegenerative diseases, e.g. Neuronal Ceroid Lipofuscinoses (NCL) (for review see [40]), which are characterized by accumulation of storage material in patients’ cells. Despite the accumulation of inclusions in many cell types, only neurons are affected resulting in increased apoptosis of neurons in patients’ central nervous system, whereas other, still dividing cells seem to be unaffected.…”

Section: Discussionsupporting

confidence: 56%

Valosin containing protein associated inclusion body myopathy: abnormal vacuolization, autophagy and cell fusion in myoblasts

Vesa

Watts

et al. 2009

Neuromuscular Disorders

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Inclusion body myopathy associated with Paget's disease and frontotemporal dementia (IBMPFD) is caused by mutations in the valosin containing protein (VCP) gene. The disease is associated with progressive proximal muscle weakness, inclusions and vacuoles in muscle fibers, malfunction in the bone remodeling process resulting in Paget disease, and premature frontotemporal dementia. VCP is involved in several cellular processes related to the endoplasmic reticulum associated degradation of proteins. To understand the pathological mechanisms underlying the myopathy in IBMPFD, we have studied the cellular consequences of VCP mutations in human primary myoblasts. Our results revealed that patients' myoblasts accumulate large vacuoles. Lysosomal membrane proteins Lamp1 and Lamp2 show increased molecular weights in patients' myoblasts due to differential Nglycosylation. Additionally, mutant myoblasts show increased autophagy when cultured in the absence of nutrients, as well as defective cell fusion and increased apoptosis. Our results elucidate that VCP mutations result in disturbances in several cellular processes, which will help us in the understanding of the pathological mechanisms resulting in muscle weakness and other features of VCP associated disease.

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Section: Discussionsupporting

confidence: 56%

Valosin containing protein associated inclusion body myopathy: abnormal vacuolization, autophagy and cell fusion in myoblasts

Vesa

Watts

et al. 2009

Neuromuscular Disorders

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“…Infantile CLN1 disease can be distinguished ultrastructurally from other forms of NCL by the accumulation of granular osmiophilic deposits in the CNS and in cultured fibroblasts. A hallmark of the NCLs, including infantile CLN1 disease, is the progressive accumulation of autofluorescent material (lipofuscin), most notably in the nervous system, but which is also found in some other tissues (Peltonen, et al 2000). Profound neuronal degeneration, cortical thinning, and overall brain atrophy are prominent features of infantile CLN1 disease (Haltia, et al 1973; Haltia, et al 1973).…”

Section: Introductionmentioning

confidence: 99%

Pathogenesis and therapies for infantile neuronal ceroid lipofuscinosis (infantile CLN1 disease)

Hawkins-Salsbury

Cooper

Sands

2013

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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The Neuronal Ceroid Lipofuscinoses (NCL, Batten Disease) are a group of inherited neurodegenerative diseases. Infantile Neuronal Ceroid lipofuscinosis (INCL, Infantile Batten Disease, or infantile CLN1 disease) is caused by a deficiency in the soluble lysosomal enzyme palmitoyl protein thioesterase-1 (PPT1) and has the earliest onset and fastest progression of all the NCLs. Several therapeutic strategies including enzyme replacement, gene therapy, stem cell-mediated therapy, and small molecule drugs have resulted in minimal to modest improvements in the murine model of PPT1-deficiency. However, more recent studies using various combinations of these approaches have shown more promising results; in some instances more than doubling the life span of PPT1-deficient mice. These combination therapies that target different pathogenic mechanisms may offer the hope of treating this profoundly neurodegenerative disorder. Similar approaches may be useful when treating other forms of NCL caused by deficiencies in soluble lysosomal proteins. Different therapeutic targets will need to be identified and novel strategies developed in order to effectively treat forms of NCL caused by deficiencies in integral membrane proteins such as Juvenile Neuronal Ceroid Lipofuscinosis. Finally, the challenge with all of the NCLs will lie in early diagnosis, improving the efficacy of the treatments, and effectively translating them into the clinic.

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“…[2] The characteristic features include mental retardation, visual impairment, progressive myoclonic epilepsy, decline in motor skills resulting in premature death. [34] Infantile and late infantile onset NCL have a poor prognosis with early deaths while juvenile and adult onset forms have a relatively better prognosis. Worldwide, these disorders are among the common lysosomal storage disorders, however, very few cases are reported from India.…”

Section: Introductionmentioning

confidence: 99%

Late infantile neuronal ceroid lipofuscinosis: A case report with review of literature

Verma

Raut

Tiwari

et al. 2013

Ann Indian Acad Neurol

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Neuronal ceroid lipofuscinosis (NCL) are a group of genetically mediated neurodegenerative disorders affecting children and young adults. They are characterized by global mental and motor deterioration, vision loss, and epilepsy ultimately resulting in death. Of the various types, late infantile variety is the 2nd most common form of NCL. Here the authors report a case of a 9-year-old boy who presented with progressive mental and social deterioration since the age of 2½ years. As the disease progressed, he developed progressive vision loss, gait ataxia, action myoclonus, and epilepsy. Electroencephalogram revealed generalized sharp and slow wave discharges with background slowing. Magnetic resonance imaging of the brain revealed diffuse cerebral and cerebellar atrophy markedly affecting the cerebellum along with periventricular T2 hyperintensities. Skin biopsy from axilla revealed characteristic intracytoplasmic eosinophilic inclusions and periodic acid Schiff positive bodies within the eccrine ducts suggestive of NCL.

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Genetics of the neuronal ceroid lipofuscinoses

Cited by 28 publications

References 60 publications

Valosin containing protein associated inclusion body myopathy: abnormal vacuolization, autophagy and cell fusion in myoblasts

Valosin containing protein associated inclusion body myopathy: abnormal vacuolization, autophagy and cell fusion in myoblasts

Pathogenesis and therapies for infantile neuronal ceroid lipofuscinosis (infantile CLN1 disease)

Late infantile neuronal ceroid lipofuscinosis: A case report with review of literature

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