The roles of the nuclear pore complex in cellular dysfunction, aging and disease

Abstract

The study of the Nuclear Pore Complex (NPC), the proteins that compose it (nucleoporins), and the nucleocytoplasmic transport that it controls have revealed an unexpected layer to pathogenic disease onset and progression. Recent advances in the study of the regulation of NPC composition and function suggest that the precise control of this structure is necessary to prevent diseases from arising or progressing. Here we discuss the role of nucleoporins in a diverse set of diseases, many of which directly or indirectly increase in occurrence and severity as we age, and often shorten the human lifespan. NPC biology has been shown to play a direct role in these diseases and therefore in the process of healthy aging.

Keywords: Aging; Cancer; Neurological; Nuclear pore complex; Nucleocytoplasmic transport; Nucleoporin.

Figure 1

Onset of nucleoporin-implicated health problems. Left: a list of the nucleoporins that are implicated in the health problems listed on the right. Right: a list of health problems with the age-based prevalence indicated by the box/triangle. Triple A: Achalasia-Addisonianism-Alacrima or Allgrove syndrome; ALS: amyotrophic lateral sclerosis; PD: Parkinson’s disease; IBSN: Infantile bilateral striatal necrosis; LCCS1: lethal congenital contracture syndrome-1; ANE: acute necrotizing encephalopathy; PBC: Primary biliary cholangitis; SRNS: steroid-resistant nephrotic syndrome