2025/05/09 by Anette Siggervåg, Åse K. Bekkelund, Jaakko Saraste +1 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Genetics and Neurodevelopmental Disorders #Peptidase Inhibition and Analysis #Signaling Pathways in Disease
paper · pdf · doi:10.1093/brain/awaf175
openalex publication_date 2025/05/09 · openalex created_date 2025/10/10 · openalex updated_date 2026/06/23
Primary familial brain calcification (PFBC) provides valuable insights into the mechanisms underlying brain calcification as it singles out the proteins that potentially are involved in the relevant cellular pathways. To date, seven genes have been linked to PFBC, and studying their encoded proteins marks an exciting new era in understanding the disease mechanisms, which may ultimately lead to therapeutic strategies to prevent brain calcification. With each new gene found to be associated with PFBC due to pathogenic variants, an additional level of understanding is achieved. Here, we highlight the most recently discovered PFBC gene, encoding the Golgi-localized N-terminal acetyltransferase NAA60. We explore the novel perspectives gained from the understanding of this enzyme's molecular, cellular and physiological properties. Interestingly, NAA60 shares a critical role with the most frequent PFBC gene, SLC20A2. Both these proteins seem to be involved in maintaining the structural integrity of the Golgi apparatus, as deficiency in either protein leads to Golgi fragmentation. Altered Golgi morphology is therefore emerging as a new significant topic in PFBC research, and we here discuss this topic in relation to existing knowledge regarding Golgi rearrangements and dysfunction as a factor in neurodegenerative diseases.