Retrotranspozomy
Retrotrasnpozomy
Elevated L1 retrotransposition
- Ataxia telangiectasia
- Rett syndrome
- Autism
- Schizophrenia
- Major depressive disorder
- Neuronal cell lines or brains of patients exposed to opioids
- Huntington's disease
- Hippocampi of mice following
- Novel exploration
- Diminished maternal care
- Amyotrophic lateral sclerosis (ALS)
- Frontotemporal dementia (FTD)
- HERV-K(HML-2) loci and increased amounts of pol gene transcripts and RT protein
- Elevated immune response to HERV-K(HML-2) Gag protein
- Envelope protein causes motor neuron toxicity and motor dysfunction in transgenic mice
- Some of the elevated RT activity observed is also due to increased expression of LINE-1 retrotransposons
- Cellular changes that increase HERV-K(HML-2) expression in ALS patients
- May similarly activate other retrotransposons
- Recent study reported global increases in expression of selected families of both LTR and non-LTR retrotransposons in ALS and FTLD patients with a hexanucleotide expansion in the Chromosome 9 Open Reading Frame 72 (C9orf72) ALS gene but not in sporadic ALS cases or controls
- Pathological aggregation of RNA-binding proteins
- ALS, FTLD, Alzheimer's disease, spinocerebellar ataxia, Huntington’s disease, and inclusion body myositis.
- ALS
- Abnormal RNA processing and abnormal self-aggregation of proteins, leading to altered RNA granule formation
- Aggregation of TAR DNA binding protein 43 (TDP-43, product of the TARDBP gene)
- Especially interesting as a unifying pathological marker of both FTLD and ALS
- Mutations in TARDBP are involved in about 4% of familial (fALS) and 1% of sporadic ALS (sALS) cases
- TDP-43 protein, while typically nuclear in healthy cells
- Is cleaved and hyperphosphorylated
- Accumulates in ubiquitinated cytoplasmic inclusions
- In almost all ALS
- In almost half of FTLD patients
- TDP-43 protein aggregation pathology also characterizes other neurodegenerative disorders
- Parkinson's
- Alzheimer's
- Huntington's
- Inclusion body myopathies
- LINE-1-encoded ORF1p are reminiscent of neurodegeneration-associated proteins
- ORF1p is
- Ubiquitinated and phosphorylated RNA-binding protein
- Prone to forming cytoplasmic aggregates
- Including SGs
- Abnormal expression of ORF1p in neuronal cells
- Might aggravate formation of cytoplasmic aggregates and contribute to disease pathology
- Some ALS-associated RNA-binding protein mutants
- Closely associate with ORF1p in cytoplasmic RNA granules of tumor cell lines
- Increasing the expression of some ALS proteins, including TDP-43
- Inhibits L1 retrotransposition in a cell culture reporter assay
- Possibility that LINE-1 retrotransposon activity may be associated with ALS disease
- Reverse transcription (RT)-qPCR) analyses failed to detect significantly altered expression of non-LTR Alu or L1 elements in sALS tissues
- By reanalyzing publicly available RNA-Seq datasets, one previously examined for TE levels [52] and one hitherto untested, we confirmed misregulation of selected TE subfamilies in C9orf72 gene-related ALS samples
