Abstract:
:In amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), spinal and lower brainstem motor neurons degenerate, but some motor neuron subtypes are spared, including oculomotor neurons (OMNs). The mechanisms responsible for this selective degeneration are largely unknown, but the molecular signatures of resistant and vulnerable motor neurons are distinct and offer clues to neuronal resilience and susceptibility. Here, we demonstrate that healthy OMNs preferentially express Synaptotagmin 13 (SYT13) compared to spinal motor neurons. In end-stage ALS patients, SYT13 is enriched in both OMNs and the remaining relatively resilient spinal motor neurons compared to controls. Overexpression of SYT13 in ALS and SMA patient motor neurons in vitro improves their survival and increases axon lengths. Gene therapy with Syt13 prolongs the lifespan of ALS mice by 14% and SMA mice by 50% by preserving motor neurons and delaying muscle denervation. SYT13 decreases endoplasmic reticulum stress and apoptosis of motor neurons, both in vitro and in vivo. Thus, SYT13 is a resilience factor that can protect motor neurons and a candidate therapeutic target across motor neuron diseases.
journal_name
Acta Neuropatholjournal_title
Acta neuropathologicaauthors
Nizzardo M,Taiana M,Rizzo F,Aguila Benitez J,Nijssen J,Allodi I,Melzi V,Bresolin N,Comi GP,Hedlund E,Corti Sdoi
10.1007/s00401-020-02133-xsubject
Has Abstractpub_date
2020-05-01 00:00:00pages
837-853issue
5eissn
0001-6322issn
1432-0533pii
10.1007/s00401-020-02133-xjournal_volume
139pub_type
杂志文章abstract::Amyloid-beta (Abeta) deposition in cerebral blood vessel walls is one of the key features of Alzheimer's disease (AD). Abeta(1-40) carrying the "Dutch" mutation (DAbeta(1-40)) induces rapid degeneration of cultured human brain pericytes (HBP). To study the mechanisms of this Abeta-induced toxicity, a comparative cDNA ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-002-0585-x
更新日期:2002-11-01 00:00:00
abstract::α-Synuclein (αSyn) histopathology defines several neurodegenerative disorders, including Parkinson's disease, Lewy body dementia, and Alzheimer's disease (AD). However, the functional link between soluble αSyn and disease etiology remains elusive, especially in AD. We, therefore, genetically targeted αSyn in APP trans...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-018-1886-z
更新日期:2018-10-01 00:00:00
abstract::Relatively little work has been done on the structural effects of organic lead in the central nervous system (CNS), although this form of lead may be a significant fraction of total brain lead. We tested a number of easily measured light-histological parameters of neuronal development in rats for sensitivity to (a) no...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00687338
更新日期:1984-01-01 00:00:00
abstract::Autopsy findings of a patient, with sialidosis type I phenotype carrying V217M/G243R mutations in the lysosomal sialidase gene and biochemically defined isolated sialidase deficiency, who died of intractable lymphoma at the age of 32 years, are described. Perikaryal expansion of cytoplasm was evident, mostly in motor ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-009-0544-x
更新日期:2010-01-01 00:00:00
abstract::The paper describes the clinical and morphological features of a congenital neurological disease affecting two in-bred litter-mate kittens. The principal neurological features were ataxia and dysmetria. In one of the kittens light microscopy revealed widespread vacuolation of white and grey matter of the brain and spi...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00690561
更新日期:1976-06-15 00:00:00
abstract::Focal cortical dysplasia (FCD) is a localized malformation of cortical development and is the commonest cause of severe childhood epilepsy in surgical practice. Children with FCD are severely disabled by their epilepsy, presenting with frequent seizures early in life. The commonest form of FCD in children is character...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-013-1135-4
更新日期:2013-08-01 00:00:00
abstract::Granule-containing vacuoles in the cytoplasm of hippocampal neurons are a neuropathological feature of Alzheimer's disease. Granulovacuolar degeneration (GVD) is not disease-specific and can be observed in other neurodegenerative disorders and even in the brains of non-demented elderly people. However, several studies...
journal_title:Acta neuropathologica
pub_type: 杂志文章,评审
doi:10.1007/s00401-016-1562-0
更新日期:2016-09-01 00:00:00
abstract::Data on the dural invasiveness of pituitary adenomas have been correlated to the expression of matrix metalloproteinases (e.g. MMP-9). Serine proteases have not yet been investigated in human pituitary adenomas. In this study, paraffin-embedded material from 84 human pituitary adenomas (acromegaly n=18, Cushing's dise...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-003-0747-5
更新日期:2003-11-01 00:00:00
abstract::This study was designed to compare the degree of reactive astrogliosis occurring around a puncture wound in the brain of normal rats and at different intervals after a similar puncture wound in rats with a portocaval anastomosis. The gliosis was evaluated by the number of astrocytes, the thickness of their processes a...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00310926
更新日期:1991-01-01 00:00:00
abstract::Dysferlin is a newly identified sarcolemmal protein related to Miyoshi myopathy and limb-girdle muscular dystrophy. Although its function is still unknown, it is inferred from the presence of C2 domains and a transmembrane domain in its sequence that dysferlin may be expressed or located not only at the sarcolemma but...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-003-0686-1
更新日期:2003-06-01 00:00:00
abstract::Rats were given isoniazid either in a single large dose or continuously in drinking water and killed 5--105 days later. The distribution of degenerating fibres in various nerves (sensory and mixed) and in various sites along nerves and spinal roots was studied by light and electron microscopy. It was found that sensor...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00691784
更新日期:1979-10-01 00:00:00
abstract::Mutations of isocitrate dehydrogenase 1 (IDH1) gene are most common in glioma, arguably preceding all known genetic alterations during tumor development. IDH1 mutations nearly invariably target the enzymatic active site Arg132, giving rise to the predominant IDH1R132H. Cells harboring IDH1 R132H -heterozygous mutation...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-017-1800-0
更新日期:2018-02-01 00:00:00
abstract::A model of hypothermic circulatory arrest with recovery has been developed in the newborn dog. Eleven puppies were anesthetized with halothane, paralyzed and artificially ventilated with 70% nitrous oxide -30% oxygen to paO2 > 60 mm Hg, paCO2 = 33-42 mm Hg and pHa = 7.35-7.42. Animals were surface cooled to 20 degrees...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00227767
更新日期:1993-01-01 00:00:00
abstract::Rat sciatic nerve was assayed for total collagen and total protein both immediately post-mortem and at weekly intervals after death. No significant difference was found in collagen and protein content between corresponding nerve segments assayed fresh and up to 4 weeks post mortem. However, variation was found in peri...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00692870
更新日期:1980-01-01 00:00:00
abstract::The differential diagnosis of Creutzfeldt-Jakob disease (CJD) from other, sometimes treatable, neurological disorders is challenging, owing to the wide phenotypic heterogeneity of the disease. Real-time quaking-induced prion conversion (RT-QuIC) is a novel ultrasensitive in vitro assay, which, at variance with surroga...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-017-1683-0
更新日期:2017-04-01 00:00:00
abstract::Intracranial germ cell tumors (iGCTs) are the second most common brain tumors among children under 14 in Japan. The World Health Organization classification recognizes several subtypes of iGCTs, which are conventionally subclassified into pure germinoma or non-germinomatous GCTs. Recent exhaustive genomic studies show...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-017-1673-2
更新日期:2017-03-01 00:00:00
abstract::An immunoperoxidase technique was used to locate synaptophysin (protein p38), a major integral membrane glycoprotein of synaptic vesicles, in the rat brain. In addition to a diffuse distribution of nerve terminal stainings for synaptophysin appearing as numerous small puncta, the large-sized cells with spindled or pol...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00304146
更新日期:1993-01-01 00:00:00
abstract::A 25-year-old homosexual AIDS patient presented with progressive cognitive, motor and behavioral disturbances consistent with HIV encephalopathy. CT scans demonstrated progressive diffuse brain atrophy. Neuropathology showed predominant cortical changes including severe neuronal loss corroborated by morphometry. Only ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00294450
更新日期:1991-01-01 00:00:00
abstract::Sera from guinea pigs with acute or chronic relapsing experimental allergic encephalomyelitis (EAE) were injected into lumbosacral subarachnoid space of normal recipient rats. Seventeen of 37 sera induced demyelination in the CNS, and 27 of 37 sera caused demyelinated peripheral nerve fibers in the roots. The highest ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00690994
更新日期:1981-01-01 00:00:00
abstract::A simple and reproducible method for cryopreservation of brain tissue from patients with Alzheimer's disease is described. Fresh brain slices (1 cm thick) obtained less than 6 h postmortem are placed in sealed plastic bags, sandwiched between 0.3-cm-thick aluminium sheets, and frozen by placing the entire "sandwich" b...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00294305
更新日期:1993-01-01 00:00:00
abstract::Axonal degeneration contributes to the transient and permanent neurological deficits seen in multiple sclerosis, an inflammatory disease of the central nervous system. To study the immunological mechanisms causing axonal degeneration, we induced experimental autoimmune encephalomyelitis (EAE) in wildtype Lewis rats an...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-006-0047-y
更新日期:2006-06-01 00:00:00
abstract::Sensitive detection of alpha-synuclein (alpha-syn) pathology is important in the diagnosis of disorders like Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy and in providing better insights into the etiology of these diseases. Several monoclonal antibodies that selectively react with aggreg...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-008-0375-1
更新日期:2008-07-01 00:00:00
abstract::Upon brain reperfusion following ischemia, there is widespread inhibition of neuronal protein synthesis that is due to phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha), which persists in selectively vulnerable neurons (SVNs) destined to die. Other investigators have shown that expression of mutant eI...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-003-0693-2
更新日期:2003-07-01 00:00:00
abstract::Monosodium-L-glutamate given subcutaneously to pregnant rats caused acute necrosis of the acetylcholinesterase-positive neurons in the area postrema. The same effect has been observed in the area postrema of fetal rats. The process of neuronal cell death and the elimination of debris by microglia cells proved to be si...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00686787
更新日期:1987-01-01 00:00:00
abstract::Immunohistochemical techniques were employed to examine the changes in free ubiquitin within the hippocampus 1, 3, 7, 14, and 30 days after a unilateral perforant pathway lesion occurred in the rat brain. Immunoreactivity for ubiquitin was remarkably decreased in the cell body and proximal dendrites of neurons through...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-001-0489-1
更新日期:2002-05-01 00:00:00
abstract::The dynamics of cell-associated Concanavalin A (Con A) in astrocytes of the newborn rat (RNA), the rat glioma (AC), and the human glioblastoma (GB) were studied in vitro by fluorescence and electron microscopy. Con A receptors on the cell surface were seen usually as a continuous thin layer, and Con A accumulations in...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00690804
更新日期:1982-01-01 00:00:00
abstract::We performed a comparative study to assess cerebral amyloid angiopathy and ApoE genotype in cases of Alzheimer's disease (AD). Ten ApoE 3,3 and ten ApoE 4,4 AD brains, as well as ten normal control brains, were selected after matching for age, sex, and duration of disease. Sections of middle frontal and inferior parie...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-006-0162-9
更新日期:2007-01-01 00:00:00
abstract::Although clinical and electrophysiological evidence indicates that the amygdaloid body plays an important role in the pathogenesis of temporal lobe epilepsy, there are very few detailed data on histopathological changes in this nucleus in epilepsy patients. In the present study we have examined the lateral nucleus of ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010050658
更新日期:1997-06-01 00:00:00
abstract::Motor neuron disease (MND) may be complicated by frontotemporal dementia and/or an extrapyramidal movement disorder. Several studies have identified the pathological substrate for dementia in MND as being ubiquitin-immunoreactive inclusions and dystrophic neurites in the extramotor neocortex and hippocampus. Although ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-003-0814-y
更新日期:2004-04-01 00:00:00
abstract::A cerebral biopsy was performed in a 39-year-old male patient with subacute paraparesis who later developed severe dementia and moderate cerebellar involvement. The histological examination showed a marked neuronal loss, severe neurofibrillary degeneration, and a great number of senile plaques. No PAS-positive plaques...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00703200
更新日期:1983-01-01 00:00:00