Peroxisomes in Neurons

Introduction to Peroxisomes

Peroxisomes refer to single membrane-bound organelles found in multiple cell types, except mature red blood cells. Its diameter ranges from 0.1 to 1 mm. Due to the lack of DNA in peroxisomes, most peroxisome membranes and matrix proteins are synthesized on free polysomes in the cytoplasm and then transported to the organelles after translation. There are two classes of matrix targeting signals for special proteins import, including peroxisomal targeting signal 1 (PTS1) and peroxisomal targeting signal 2 (PTS2). The marked plasticity makes them move in a motor protein-dependent manner in mammals, plants, and fungi. In humans, they are mainly found in the brain, heart, kidney, and liver. Peroxisomes contain almost 50 different proteins in mammals for a series of anabolic and catabolic reactions. However, the shape, number, and enzymatic content are different between tissues and organisms and even upon changes in the environment.

Fig.1 Identification of peroxisomes in neural cells. (Trompier, 2014)

Functions of Peroxisomes in Neurons

Peroxisomes contain a variety of enzymatic activities which are important for mammalian physiology. The major functions include lipid peroxidation and β-oxidation of very long-chain fatty acids. In the central nervous system (CNS), peroxisomes can synthesize ether phospholipids in neurons and glial, as well as lipids that makeup myelin and cell membranes. The division and maintenance of peroxisomes are regulated with the endoplasmic reticulum and mature on the substrate and membrane.

Fig.2 Schematic representation of abnormalities of myelinated axons and synaptic transmission in peroxisomal deficiencies. (Berger, 2016)

In recent years, some studies have shown that the absence of a single enzyme, transporter functions, or all peroxisome functions would lead to aberrant brain development, loss of axonal integrity, neuroinflammation, and even severe neurological deficits. These diseases are also called peroxisome biogenesis disorders (PBD) with symptoms of rhizomelic chondrodysplasia punctata (RCDP) type 1and Zellweger spectrum disorders. What’s more, the potential role in brain degeneration has been served to be involved in cell senescence and the development of Alzheimer's disease.

In conclusion, peroxisomes play important roles in the maintenance of the CNS, the further research may focus on the treatment of neurological diseases and maintenance of cell homeostasis.

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References

1. Trompier, D. et al. Brain peroxisomes. Biochimie. 2014, 98: 102-110.
2. Berger, J.; et al. Peroxisomes in brain development and function. Biochimica Et Biophysica Acta (BBA)-Molecular Cell Research. 2016, 1863(5): 934-955.