Inclusion body myositis, viral infections, and TDP-43: a narrative review

Area of Science:

• Neurology
• Immunology
• Molecular Biology

Background:

• TDP-43, an RNA-processing protein, is implicated in neuromuscular disorders like inclusion body myositis.
• Viral infections can impair TDP-43 solubility and function.
• Inclusion body myositis is a late-onset inflammatory myopathy.

Purpose of the Study:

• To explore the connection between viral infections, TDP-43 dysfunction, and inclusion body myositis pathogenesis.
• To investigate the role of age-shaped immune responses in viral contributions to inclusion body myositis.

Main Methods:

• Review of existing literature on TDP-43, viral infections, and immune responses in neuromuscular diseases.
• Analysis of proposed mechanisms linking viral factors, interferon signaling, and T cell activity to myositis.

Main Results:

• Viral infections, co-infections, and latent virus reactivation are potential triggers for inclusion body myositis.
• Senescent, interferon-gamma-producing cytotoxic CD8+ T cells are implicated in disease occurrence.
• Age-related immune changes may influence susceptibility.

Conclusions:

• Viral infections and aberrant immune responses, especially involving cytotoxic T cells, are hypothesized to drive inclusion body myositis by affecting TDP-43.
• Further research into virus-interferon-neuromuscular degeneration pathways may illuminate TDP-43-related diseases and suggest therapies.