NCL disease mechanisms

TY - JOUR

T1 - NCL disease mechanisms

AU - Palmer, David N.

AU - Barry, Lucy A.

AU - Tyynela, Jaana

AU - Cooper, Jonathan D.

PY - 2013/11

Y1 - 2013/11

N2 - Despite the identification of a large number of disease-causing genes in recent years, it is still unclear what disease mechanisms operate in the neuronal ceroid lipofuscinoses (NCLs, Batten disease). As a group they are defined by the specific accumulation of protein, either subunit c of mitochondrial ATP synthase or SAPs A and D in lysosome-derived organelles, and regionally specific neurodegeneration. Evidence from biochemical and cell biology studies indicates related lesions in intracellular vesicle trafficking and lysosomal function. There is also extensive immunohistological evidence of a causative role of disease associated neuroinflammation. However the nature of these lesions is not clear nor is it clear why they lead to the defining pathology. Several different theories have proposed a range of potential mechanisms, but it remains to be determined which are central to pathogenesis, and whether there is a mechanism consistent across the group, or if it differs between disease forms. This review summarises the evidence that is currently available and the progress that has been made in understanding these profoundly disabling disorders. This article is part of a Special Issue entitled: The Neuronal Ceroid Lipofuscinoses or Batten Disease.

AB - Despite the identification of a large number of disease-causing genes in recent years, it is still unclear what disease mechanisms operate in the neuronal ceroid lipofuscinoses (NCLs, Batten disease). As a group they are defined by the specific accumulation of protein, either subunit c of mitochondrial ATP synthase or SAPs A and D in lysosome-derived organelles, and regionally specific neurodegeneration. Evidence from biochemical and cell biology studies indicates related lesions in intracellular vesicle trafficking and lysosomal function. There is also extensive immunohistological evidence of a causative role of disease associated neuroinflammation. However the nature of these lesions is not clear nor is it clear why they lead to the defining pathology. Several different theories have proposed a range of potential mechanisms, but it remains to be determined which are central to pathogenesis, and whether there is a mechanism consistent across the group, or if it differs between disease forms. This review summarises the evidence that is currently available and the progress that has been made in understanding these profoundly disabling disorders. This article is part of a Special Issue entitled: The Neuronal Ceroid Lipofuscinoses or Batten Disease.

KW - Pathogenesis

KW - Selective neuron loss

KW - Glial activation

KW - Synaptic pathology

KW - Storage material accumulation

KW - Biochemical abnormalities

KW - NEURONAL-CEROID-LIPOFUSCINOSIS

KW - PALMITOYL-PROTEIN THIOESTERASE

KW - MITOCHONDRIAL ATP SYNTHASE

KW - JUVENILE BATTEN-DISEASE

KW - TRIPEPTIDYL-PEPTIDASE-I

KW - CATHEPSIN-D DEFICIENCY

KW - SOUTH HAMPSHIRE SHEEP

KW - MANNOSE 6-PHOSPHATE GLYCOPROTEOME

KW - LYSOSOMAL STORAGE DISEASE

KW - CENTRAL-NERVOUS-SYSTEM

U2 - 10.1016/j.bbadis.2013.05.014

DO - 10.1016/j.bbadis.2013.05.014

M3 - Literature review

SN - 0925-4439

VL - 1832

SP - 1882

EP - 1893

JO - BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

JF - BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

IS - 11

M1 - N/A

ER -