IISER MOHALI

Abstract: Aging is an inevitable process through which our brain and body undergo progressive changes, some of which have highly unfavorable outcomes. Many of the neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, and Frontotemporal dementia, are caused by the loss of many neurons in the functional brain circuits. One approach to treat these conditions is to introduce new neurons, which can further integrate into the functional circuitry. It has been a long-standing problem for clinicians to find a cure for patients with nervous system injuries or degeneration due to failure of neurite regeneration in the central nervous system and the re-establishment of functional connections with target tissues.

Our group at the National Brain Research Center has been investigating the molecular mechanism of axon regeneration. Axons are long cables through which nerve cells propagate electrical signals to their post-synaptic neurons. We have identified a conserved signalling pathway involving Dual Leucine Zipper Kinase (DLK) that is required for axon regeneration following injury. We have further shown that axon regeneration leads to functional restoration in the early stages of life, and this ability is lost in old age. Manipulation of the conserved let-7 miRNA or Insulin (IIS) signalling can overcome age-related decline in axon regeneration and aid in functional recovery.

Recently, we found that dendrites (the information-receiving units of neurons) can also regenerate following physical injury. However, the axon regeneration pathway DLK is not required for dendrite regeneration. This suggested that the molecular mechanism underlying dendrite regeneration is distinct from that of axonal regeneration.

Collectively, our findings significantly advance the fundamental understanding of neurite repair and functional reconnection.