The Bcl-2 Homology-3 Domain (BH3)-Only Proteins, Bid, DP5/Hrk, and BNip3L, Are Upregulated in Reactive Astrocytes of End-Stage Mutant SOD1 Mouse Spinal Cord

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The Bcl-2 Homology-3 Domain (BH3)-Only Proteins, Bid, DP5/Hrk, and BNip3L, Are Upregulated in Reactive Astrocytes of End-Stage Mutant SOD1 Mouse Spinal Cord

The molecular mechanisms leading to motor neuron death in amyotrophic lateral sclerosis (ALS) are unknown; however, several studies have provided evidence of a central role for intrinsic apoptosis. Bcl-2 homology-3 domain (BH3)-only proteins are pro-apoptotic members of the Bcl-2 family whose enhanced expression acts as a trigger for the intrinsic apoptotic cascade. Here, we compared the relati...

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Role of the BH3 (Bcl-2 homology 3) domain in the regulation of apoptosis and Bcl-2-related proteins.

The Bcl-2 family of proteins play a prominent role in the regulation of apoptosis. From the initial identification of bcl-2 as an oncogene in follicular lymphoma through genetic studies in Caenorhabditis elegans to recent functional studies focusing on the importance of mitochondrial events in cell death signalling, the members of this protein family continue to be implicated in pivotal decisio...

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Amyotrophic Lateral Sclerosis-Associated SOD1 Mutant Proteins Bind and Aggregate with Bcl-2 in Spinal Cord Mitochondria

Familial amyotrophic lateral sclerosis (ALS)-linked mutations in the copper-zinc superoxide dismutase (SOD1) gene cause motor neuron death in about 3% of ALS cases. While the wild-type (wt) protein is anti-apoptotic, mutant SOD1 promotes apoptosis. We now demonstrate that both wt and mutant SOD1 bind the anti-apoptotic protein Bcl-2, providing evidence of a direct link between SOD1 and an apopt...

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ALS-linked mutant SOD1 damages mitochondria by promoting conformational changes in Bcl-2

In mutant superoxide dismutase (SOD1)-linked amyotrophic lateral sclerosis (ALS), accumulation of misfolded mutant SOD1 in spinal cord mitochondria is thought to cause mitochondrial dysfunction. Whether mutant SOD1 is toxic per se or whether it damages the mitochondria through interactions with other mitochondrial proteins is not known. We previously identified Bcl-2 as an interacting partner o...

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The BH3 domain of Bcl-2 proteins was regarded as indispensable for apoptosis induction and for mutual regulation of family members. We recently described Bcl-x(AK), a proapoptotic splice product of the bcl-x gene, which lacks BH3 but encloses BH2, BH4 and a transmembrane domain. It remained however unclear, how Bcl-x(AK) may trigger apoptosis.For efficient overexpression, Bcl-x(AK) was subclone...

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ژورنال

عنوان ژورنال: Frontiers in Cellular Neuroscience

سال: 2018

ISSN: 1662-5102

DOI: 10.3389/fncel.2018.00015