FUS-immunoreactive intranuclear inclusions in neurodegenerative disease.

Neuronal intranuclear inclusions (NIIs) are a histopathological hallmark of several neurodegenerative disorders. However, the role played by NIIs in neurodegenerative pathogenesis remains enigmatic. Defining their molecular composition represents an important step in understanding the pathophysiology of these disorders.

Promyelocytic leukaemia-immunoreactive neuronal intranuclear rodlets in the human brain.

In a previous study, we demonstrated immunoreactivity of a subset of neuronal intranuclear rodlets (INRs) in the human substantia nigra for promyelocytic leukaemia (PML) protein, the signature protein of PML bodies. In the present study, we extend these observations and describe the ultrastructural features, immunohistochemical staining characteristics, and topographical pattern of distribution of PML-immunoreactive intranuclear rodlets (PML-INRs). Consistent with a purported role for PML bodies in nuclear proteolysis and/or transcriptional regulation, PML-INRs are immunoreactive for components of the ubiquitin-proteasome system, the transcriptional regulator CREB-binding protein, acetylated histone H4, and the eukaryotic translation initiation factor eIF4E.

Abnormalities of the nucleus and nuclear inclusions in neurodegenerative disease: a work in progress.

Neurodegenerative diseases are characterized pathologically by the abnormal accumulation of pathogenic protein species within the cell. Several neurodegenerative diseases feature intranuclear protein aggregation in the form of intranuclear inclusion bodies. Studies of these intranuclear inclusions are providing important clues regarding the cellular pathophysiology of these diseases, as exemplified by recent progress in defining the genetic basis of a subset of frontotemporal dementia cases.

Intranuclear rodlets in the substantia nigra: interactions with marinesco bodies, ubiquitin, and promyelocytic leukemia protein.

There is growing appreciation that the nucleus is organized into an array of discrete structural domains, each subserving a specific function. These functional nuclear bodies are to be distinguished from pathological intranuclear inclusions which have been described in a variety of neurodegenerative diseases. Marinesco bodies (MBs) are eosinophilic ubiquitinated intranuclear inclusions found in pigmented neurons of the human substantia nigra and locus coeruleus.

Reduction of neuronal intranuclear rodlets immunoreactive for tubulin and glucocorticoid receptor in Alzheimer's disease.

Neuronal intranuclear rodlets were described in normal brain over a century ago, but their functional significance and pathological relevance is unknown. Here, we show co-localization of tubulin and glucocorticoid receptor-like immunoreactivity in these intranuclear inclusions in human brain. In addition, we provide evidence for a massive reduction in their areal density in Alzheimer's disease brain, but not in another common neurodegenerative condition, dementia with Lewy bodies.

Frontotemporal dementia with ubiquitinated cytoplasmic and intranuclear inclusions.

Dementia of motor neuron disease type (DMND) is a variety of frontotemporal dementia (FTD) which is pathologically defined by characteristic neuronal ubiquitinated, tau- and synuclein-negative intracytoplasmic inclusions. Many cases with this pathology, however, do not have motor neuron disease. In the present study, we document the presence of ubiquitinated neuronal intranuclear inclusions in a sub-population of cases of neuropathologically verified DMND.

Monoclonal antibodies against Epstein-Barr virus cross-react with alpha-synuclein in human brain.

Using antibodies generated against the latent membrane protein 1 of Epstein-Barr virus, intense immunoreactivity of Lewy bodies (in PD and dementia with Lewy bodies) and glial cytoplasmic inclusions (in multiple system atrophy) was demonstrated. ELISA and Western blotting techniques confirmed that this immunolabeling was due to cross-reactivity of the antiviral antibody with alpha-synuclein, a neuronal protein implicated in the pathogenesis of PD. This example of cross-reactivity between Epstein-Barr virus and alpha-synuclein may bear implications for further elucidating infectious or autoimmune mechanisms in PD.

Class III beta-tubulin immunoreactive intranuclear inclusions in human ependymomas and gangliogliomas.

We have observed intranuclear inclusion bodies immunoreactive for the cytoskeletal protein class III beta tubulin (C3betaT) in neurons and ependymal cells of post-mortem human brain. The relationship of these inclusions, detected by light microscopy, to the intranuclear rodlets described by the classical microscopists is unknown. The present study was conducted to determine whether these proteinaceous inclusions (C3betaT-NIIs) exist in the neoplastic counterparts of these cell types.