Dr. Van Zundert invites us on an enlightening journey into the intricate world of neurodegenerative diseases, specifically amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). These disorders have puzzled researchers for years, especially given the involvement of non-cell-autonomous mechanisms where toxic factors released by astrocytes lead to motorneuron (MN) damage. The heart of this mystery? A compound known as inorganic polyphosphate (polyP).

Delving deep into his research, Dr. Van Zundert unveils a startling discovery. Astrocytes derived from mice and patient-induced pluripotent stem cells (iPSCs) with mutations linked to ALS/FTD (including SOD1, TARDBP, and C9ORF72) exhibit a spike in their intracellular polyP levels. The consequence? Elevated polyP levels in astrocyte-conditioned media (ACM), which, when presented t ...