Additional homozygous variants were identified, including the risk allele p.Arg261His in NEK1, as well as variants in genes known to be associated with other neurodegenerative diseases, such as HTT (Huntington's disease), ATM (Ataxia-Telangiectasia), and ZFYVE26 (SPG15), and variants in genes previously reported as upregulated (LZTS3) or downregulated (ARMC4, CFAP54, and MTHFSD) in ALS patients.
Ataxia-telangiectasia (A-T) is a rare neurodegenerative disease, due to A-T mutated (ATM) gene mutations, which typically presents with signs of progressive neurological dysfunction, cerebellar ataxia and uncoordinated movements.
ATM associates with organelles including mitochondria and peroxisomes, both sources of reactive oxygen species (ROS), which have been implicated in neurodegenerative diseases and aging.
Although the majority of studies indicate a neuroprotective action for the inhibition of angiotensin converting enzyme or blockade of AT1 receptor, recent studies point to the participation of other angiotensin peptides in the pathophysiology of the neurodegenerative diseases.
Ataxia telangiectasia (A-T) is a rare incurable neurodegenerative disease caused by biallelic mutations in the gene for ataxia-telangiectasia mutated (ATM).
In the present review, we summarized the clinical presentations and biology backgrounds of NDs, including Parkinson's disease (PD), Huntington's disease (HD), and Alzheimer's disease (AD) and explored the role of molecular mechanisms, including dys-regulation of epigenetic control mechanisms, Ataxia-telangiectasia-mutated protein kinase (ATM), and neuroinflammation in the pathogenesis of NDs.
Finally, the decline of ATM levels with age suggest that late onset neurodegenerative diseases may owe part of their pathogenesis to deficits in ATM signaling.
Ataxia-telangiectasia (A-T) is an autosomal recessive neurodegenerative disorder with multisystem involvement and cancer predisposition, caused by mutations in the A-T mutated (ATM) gene.
In addition to delineating the biochemistry and cell biology of ATM, important insights into the molecular basis for neurodegeneration in A-T come from a spectrum of phenotypically related neurodegenerative diseases that directly result from DNA-repair deficiency.
Mutations in the ATM kinase cause the neurodegenerative disorder ataxia telangiectasia (A-T) and affected individuals are exquisitely radiation-sensitive and cancer-prone.