Parthanatos as a Cell Death Pathway Underlying Retinal Disease

Scott H Greenwald; Eric A Pierce

doi:10.1007/978-3-030-27378-1_53

Parthanatos as a Cell Death Pathway Underlying Retinal Disease

Adv Exp Med Biol. 2019:1185:323-327. doi: 10.1007/978-3-030-27378-1_53.

Authors

Scott H Greenwald¹, Eric A Pierce²

Affiliations

¹ Ocular Genomics Institute, Department of Ophthalmology, Massachusetts Eye & Ear, Harvard Medical School, Boston, MA, USA. scott_greenwald@meei.harvard.edu.
² Ocular Genomics Institute, Department of Ophthalmology, Massachusetts Eye & Ear, Harvard Medical School, Boston, MA, USA.

Abstract

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.

Keywords: Apoptosis-inducing factor; Bioenergetics; NAD+; PAR; PARP1; Parthanatos; Programmed cell death.

Publication types

Review

MeSH terms

Apoptosis Inducing Factor
Humans
Parthanatos*
Poly (ADP-Ribose) Polymerase-1 / genetics
Poly Adenosine Diphosphate Ribose
Protein Transport
Retinal Diseases / pathology*

Substances

Apoptosis Inducing Factor
Poly Adenosine Diphosphate Ribose
PARP1 protein, human
Poly (ADP-Ribose) Polymerase-1

Grants and funding

R01 EY012910/EY/NEI NIH HHS/United States