Question

How are the molecular pathways that control apoptosis and axonal pruning similar and different?

Answer 1

Ans.

Apoptosis versus axon pruning: Molecular intersection of two distinct pathways for axon degeneration

• Neuronal apoptosis and axon pruning engage distinct pathways to mediate axon degeneration.
• Apoptosis and axon pruning both involve DLK/JNK signaling, Puma and Bax.
• Apoptosis requires caspases (Casp9, Casp3) that are activated via the Apaf-1 apoptosome.
• Axon pruning requires Casp9, Casp3, and also Casp6, but not the Apaf-1 apoptosome.

Metabolic aspects of neuronal degeneration: from a NAD+ point of view.

• Dysregulations of cellular metabolism play important roles in neurodegeneration.
• Axonal degeneration is a crucial component of neurodegeneration.
• NAD + metabolism governs axonal degeneration.

Regulation of neuronal/axonal degeneration by ZNRF1 ubiquitin ligase

• ZNRF1 is an E3 ubiquitin ligase expressed in most neurons in both CNS and PNS.
• ZNRF1-AKT-GSK3B-CRMP2 pathway regulates the progression of Wallerian degeneration.
• ZNRF1 becomes activated by EGFR-dependent phosphorylation in response to oxidative stress.
• ZNRF1 can elicit signaling for inducing axonal degeneration and apoptosis in neurons.
• GSK3B-dependent phosphorylation of MCL1 induces autophagy to promote axonal degeneration.

Translating regeneration: Local protein synthesis in the neuronal injury response

• Local translation contributes to retrograde injury signaling and axon regeneration.
• Numerous mRNAs localize to axons in different neuron types.
• Diverse sources have been proposed for axonal ribosomes.
• mTOR and other kinases drive local translation in axons.

B lymphocytes: Crucial contributors to brain development and neurological diseases

• B cells have diverse functions in brain development and neurological diseases.
• B-1a cells are involved in oligodendrocyte development.
• B cells play detrimental roles in neurological diseases.
• Regulatory B cells suppress inflammation in pathological conditions.

Mitochondrial behavior during axon regeneration/degeneration in vivo

• Mitochondrial behavior in an axon reflects axonal condition.
• Increased supply of healthy mitochondria facilitates axon regeneration.
• In vivo imaging of mitochondrial dynamics in lesioned axon provides a new insight.

Axonal and neuronal degeneration in myelin diseases

• Axonal and neuronal degeneration causes neurological defects in myelin diseases.
• Inflammation and oxidative stress increase degeneration.
• Impaired axonal and neuronal metabolism is implicated in degeneration.
• Axonal and neuronal metabolism depends on mitochondrial functions and dynamics