Abstract:
:Toxicity associated with abnormal protein folding and protein aggregation are major hypotheses for neurodegeneration. This article comparatively reviews the experimental and human tissue-based evidence for the involvement of such mechanisms in neuronal death associated with the motor system disorders of X-linked spinobulbar muscular atrophy (SBMA; Kennedy's disease) and amyotrophic lateral sclerosis (ALS), especially disease related to mutations in the superoxide dismutase (SOD1) gene. Evidence from transgenic mouse, Drosophila and cell culture models of SBMA, in common with other trinucleotide repeat expansion disorders, show protein aggregation of the mutated androgen receptor, and intraneuronal accumulation of aggregated protein, to be obligate mechanisms. Strong experimental data link these phenomena with downstream biochemical events involving gene transcription pathways (CREB-binding protein) and interactions with protein chaperone systems. Manipulations of these pathways are already established in experimental systems of trinucleotide repeat disorders as potential beneficial targets for therapeutic activity. In contrast, the evidence for the role of protein aggregation in models of SOD1-linked familial ALS is less clear-cut. Several classes of intraneuronal inclusion body have been described, some of which are invariably present. However, the lack of understanding of the biochemical basis of the most frequent inclusion in sporadic ALS, the ubiquitinated inclusion, has hampered research. The toxicity associated with expression of mutant SOD1 has been intensively studied however. Abnormal protein aggregation and folding is the only one of the four major hypotheses for the mechanism of neuronal degeneration in this disorder currently under investigation (the others comprise oxidative stress, axonal transport and cytoskeletal dysfunctions, and glutamatergic excitotoxicity). Whilst hyaline inclusions, which are strongly immunoreactive to SOD1, are linked to degeneration in SOD1 mutant mouse models, the evidence from human tissue is less consistent and convincing. A role for mutant SOD1 aggregation in the mitochondrial dysfunction associated with ALS, and in potentially toxic interactions with heat shock proteins, both leading to apoptosis, are supported by some experimental data. Direct in vitro data on mutant SOD1 show evidence for spontaneous oligomerization, but the role of such oligomers remains to be elucidated, and therapeutic strategies are less well developed for this familial variant of ALS.
journal_name
Neuropathol Appl Neurobioljournal_title
Neuropathology and applied neurobiologyauthors
Wood JD,Beaujeux TP,Shaw PJdoi
10.1046/j.0305-1846.2003.00518.xkeywords:
subject
Has Abstractpub_date
2003-12-01 00:00:00pages
529-45issue
6eissn
0305-1846issn
1365-2990pii
518journal_volume
29pub_type
杂志文章,评审abstract::Brains from human fetuses of 13 to 27 weeks gestation have been examined immunohistologically for the presence of macrophages using the marker alpha-1-anti-chymotrypsin. A preliminary study demonstrated this to be a satisfactory marker of brain macrophages, although macrophages were also weakly positive for the more s...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1991.tb00738.x
更新日期:1991-10-01 00:00:00
abstract:AIMS:Resident and peripherally derived glioma associated microglia/macrophages (GAMM) play a key role in driving tumour progression, angiogenesis, invasion and attenuating host immune responses. Differentiating these cells' origins is challenging and current preclinical models such as irradiation-based adoptive transfe...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12489
更新日期:2019-02-01 00:00:00
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journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1983.tb00131.x
更新日期:1983-11-01 00:00:00
abstract::A quantitative assessment was made of the myogenic capability in vitro of muscle cells from dystrophic (129 Rej dy/dy) and normal mice from birth to 5 months old. Seeding efficiency was increased in dystrophic cells from neonatal and 1-week-old mice compared to age-matched controls. The extent of myogenesis in culture...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1981.tb00098.x
更新日期:1981-07-01 00:00:00
abstract:AIMS:Much evidence demonstrates that Toll-like receptor-4 (TLR4)-mediated microglial activation is an important contributor to the inflammatory injury in intracerebral haemorrhage (ICH). However, the exact mechanism of TLR4-mediated microglial activation induced by ICH is not clear. In addition, microglial autophagy is...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12177
更新日期:2015-06-01 00:00:00
abstract::The relationships between the degree of cortical prion protein (PrP) deposition, tissue vacuolation and astrocytosis were studied in the frontal cortex of 27 cases of human spongiform encephalopathy, encompassing 13 cases of sporadic Creutzfeldt-Jakob disease (sCJD), four cases of familial CJD (fCJD) (one owing to E20...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1046/j.1365-2990.2003.00486.x
更新日期:2003-10-01 00:00:00
abstract:BACKGROUND:In definite Creutzfeldt-Jakob disease (CJD), morphological and immunohistochemical patterns are useful to identify molecular subtypes. Severe cerebellar pathology and hippocampal involvement helps to identify VV subtypes. The rare VV1 variant (<1%), more frequent in young individuals, is additionally charact...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2011.01208.x
更新日期:2012-04-01 00:00:00
abstract:AIMS:The secondary dystroglycanopathies represent a heterogeneous group of congenital muscular dystrophies characterized by the defective glycosylation of alpha dystroglycan. These disorders are associated with mutations in at least 17 genes, including Fukutin-related protein (FKRP). At the severe end of the clinical s...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
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更新日期:2017-06-01 00:00:00
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journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2007.00932.x
更新日期:2008-10-01 00:00:00
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journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1046/j.0305-1846.2000.00289.x
更新日期:2000-12-01 00:00:00
abstract::Clinicopathological observations suggest there is considerable overlap between vascular dementia (VaD) and Alzheimer's disease (AD). We used immunochemical methods to compare quantities of amyloid-beta (Abeta) peptides in post mortem brain samples from VaD, AD subjects and nondemented ageing controls. Total Abeta pept...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2006.00696.x
更新日期:2006-04-01 00:00:00
abstract::Mitochondrial dysfunction leads to oxygen free radical (ROS) generation with consequent oxidative stress and cellular damage. Recently, activation of the cellular antioxidant system and apoptosis were demonstrated in skeletal muscle fibres from patients with mitochondrial diseases, but the underlying mechanisms remain...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1046/j.1365-2990.2003.00411.x
更新日期:2003-02-01 00:00:00
abstract::The organization of astrocytes in myelinated culture of mouse spinal cord tissue was analysed ultrastructurally and compared with the pattern in vivo. Astrocyte cell bodies and their processes, connected by punctate adhesions and gap junctions, formed a continuous layer around the entire explant. Throughout the parenc...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1984.tb00390.x
更新日期:1984-11-01 00:00:00
abstract::Fibre type differentiation was carried out on 20 biopsies from Duchenne Muscular Dystrophy (DMD) sufferers using the acid-preincubated reaction for myofibrillar ATPase. Fibres, classified as either type 1, type 2 or 2C, were counted and their minimum diameters (least fibre axis) measured. Particular attention was paid...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1985.tb00039.x
更新日期:1985-11-01 00:00:00
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journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2990.1985.tb00007.x
更新日期:1985-03-01 00:00:00
abstract:BACKGROUND:Juvenile neuronal ceroid lipofuscinoses (JNCL) or juvenile Batten disease is a recessively inherited childhood neurodegenerative disorder resulting from a mutation in CLN3, which encodes a putative lysosomal protein of unknown function. AIM:Recent evidence suggests that a disruption in CLN3 function results...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2008.00984.x
更新日期:2009-04-01 00:00:00
abstract:AIM:Pilocytic astrocytomas represent the most common paediatric tumours of the central nervous system. Dissemination through the ventricular system occurs rarely in patients with pilocytic astrocytomas; however, it is more common in infants with diencephalic tumours, and is associated with a poor outcome. Despite histo...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12256
更新日期:2016-04-01 00:00:00
abstract:AIM:Borna disease virus (BDV) induces a persistent infection in the central nervous system (CNS) accompanied by a non-purulent meningoencephalitis. BDV-infection of Lewis rats provides an important model to investigate basic principles of neurotropism, viral persistence and resulting dysfunctions. To date, the in vivo ...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2008.00940.x
更新日期:2008-12-01 00:00:00
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journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章,评审
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更新日期:2018-02-01 00:00:00
abstract::Changes of 5'-nucleotidase (5'-N) activity during subcultivation of C6 clonal rat glioma cells were studied histochemically, cytochemically and biochemically. Two different cell populations were seeded with high or low cell density respectively. 5'-N activity in cultured cells increased continuously in both population...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1985.tb00014.x
更新日期:1985-05-01 00:00:00
abstract::The cellular distribution of the lysosomal proteinase cathepsin D was studied in a series of 76 neoplasms and 18 non-neoplastic tissues from the human central nervous system, using a well-characterized polyclonal antibody in a peroxidase-antiperoxidase technique. In the normal and developing brain, cathepsin D is conf...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1990.tb00930.x
更新日期:1990-02-01 00:00:00
abstract::This paper continues the historical review on the concept of a sensorimotor cortex into the twentieth century. Paul Flechsig was probably the first to accept this concept after the turn of the century. Like Munk, he believed in an almost reflex-like unity between cortical sensory and motor function. With the help of h...
journal_title:Neuropathology and applied neurobiology
pub_type: 历史文章,杂志文章
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更新日期:1982-03-01 00:00:00
abstract:AIMS:Infection of the mouse central nervous system with wild type (WT) and vaccine strains of measles virus (MV) results in lack of clinical signs and limited antigen detection. It is considered that cell entry receptors for these viruses are not present on murine neural cells and infection is restricted at cell entry....
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2009.01023.x
更新日期:2009-10-01 00:00:00
abstract::We have examined the influence that axons may have on the expression of proteolipid protein (PLP), the major myelin protein of the CNS. Partial transections were made of the optic nerve of adult rats to produce approximately a 50% loss of axons. Twenty-eight days after lesioning, sections of the distal nerves were imm...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1991.tb00725.x
更新日期:1991-08-01 00:00:00
abstract:AIMS:Phosphorylated TDP-43 (pTDP-43) is the pathological protein responsible for amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease. Recently, it has been reported that accumulation of pTDP-43 can occur in the brains of patients with argyrophilic grain disease (AGD), in which phosphorylated 4-repeat...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2011.01175.x
更新日期:2012-02-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is a fatal devastating neurodegenerative disorder which predominantly affects the motor neurons in the brain and spinal cord. The death of the motor neurons in ALS causes subsequent muscle atrophy, paralysis and eventual death. Clinical and biological evidence now demonstrates that ...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章,评审
doi:10.1111/nan.12206
更新日期:2015-08-01 00:00:00
abstract:AIMS:This study explores the neuroprotective effects and mechanisms of N-acetyl-L-cysteine (NAC) in mice exposed to cadmium (Cd). METHODS:NAC (150 mg/kg) was intraperitoneally administered to mice exposed to Cd (10-50 mg/L) in drinking water for 6 weeks. The changes of cell damage and death, reactive oxygen species (R...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12103
更新日期:2014-10-01 00:00:00
abstract::Dysfunction of the ubiquitin-dependent proteolytic pathway contributes to progressive accumulation of ubiquitinated protein inclusions in neurodegenerative disorders, such as Parkinson's disease (PD). Ubiquitin C-terminal hydrolase-L1 (UCH-L1), alternatively designated protein gene product 9.5 (PGP9.5), is a neural de...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1046/j.1365-2990.2001.00313.x
更新日期:2001-04-01 00:00:00
abstract::A demyelinating perivascular condition has been observed in the optic nerves of three cats, the lesions of which included the following features: thinly myelinated and demyelinated axons, few normal oligodendrocytes, astroglial scar tissue, lymphocytes, plasma cells, mononuclear phagocytic cells and lipid-laden cells....
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1979.tb00638.x
更新日期:1979-09-01 00:00:00
abstract::Medulloblastomas (MBs) are malignant primitive neuroectodermal tumours (PNETs) of the cerebellum occurring predominantly in childhood. The association of monosomy of chromosome 22 with MB is controversial. Atypical teratoid/rhabdoid tumours (AT/RTs) of the brain share clinical and histological features with MBs and su...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1046/j.1365-2990.2002.00388.x
更新日期:2002-04-01 00:00:00