Parthanatos as a Cell Death Pathway Underlying Retinal Disease

• Published in: Advances in experimental medicine and biology Vol. 1185; p. 323
• Main Authors: Greenwald, Scott H, Pierce, Eric A
• Format: Journal Article
• Language: English
• Published: United States 2019
• Subjects: Apoptosis Inducing Factor; Humans; Parthanatos; Poly (ADP-Ribose) Polymerase-1 - genetics; Poly Adenosine Diphosphate Ribose; Protein Transport; Retinal Diseases - pathology; NAD; PAR; Bioenergetics; PARP1; Apoptosis-inducing factor; Programmed cell death; Parthanatos
• ISSN: 0065-2598
• DOI: 10.1007/978-3-030-27378-1_53

Parthanatos is a programmed cell death pathway mediated by the effects of pathogenically high levels of poly(ADP-ribose) polymerase 1 (PARP1) activity. This process underlies a broad range of diseases affecting many tissues and organs across the body, including the retina. This chapter reviews mechanisms that are currently understood to drive parthanatos in the context of retinal diseases associated with this form of cell death. Toxicity of upregulated poly(ADP-ribose) (PAR) content, NAD and ATP depletion, translocation of apoptosis-inducing factor (AIF) to the nucleus, and loss of glycolytic function are discussed. Since therapies that preserve vulnerable cells remain elusive for the vast majority of retinal diseases, pharmacologically blocking parthanatos may be an effective treatment strategy for cases in which this process contributes to pathogenesis.