Protein damage is caused by a variety of factors, including internal processes and external influences. These factors often work in concert, leading to the misfolding and dysfunction of proteins, ultimately harming cells and tissues.
Internal Causes of Protein Damage:
- Aging: As we age, mutations and thermodynamic instability contribute to protein misfolding. ([Reference: PMC6451363]) This natural process gradually increases the likelihood of errors during protein synthesis and folding.
- Genetic Mutations: Genetic errors can lead to the production of proteins with altered structures, making them prone to misfolding or aggregation. For example, a pathogenic missense variant in the NFKB1 gene can cause common variable immunodeficiency due to detrimental protein damage. ([Reference: PubMed 33995346])
- Protein Misfolding: Incorrectly folded proteins can disrupt cellular processes and cause damage. Prion diseases, for example, are caused by misfolded PrP proteins which accumulate in the brain, leading to brain cell damage. ([References: NIH News Release June 11, 2009; Johns Hopkins Medicine on Prion Diseases]) In Alzheimer's disease, amyloid precursor proteins misfold, contributing to neuronal damage. ([Reference: NIA on Alzheimer's])
External Causes of Protein Damage:
- Infectious Agents: Viruses, such as coronaviruses, can directly damage cells and cause inflammation through their spike proteins. This inflammation can lead to further protein damage. ([Reference: American Heart Association News])
- Environmental Factors: Oxidative stress from environmental toxins can damage proteins, altering their structure and function.
Consequences of Protein Damage:
Damage to proteins can manifest in various ways, depending on the type and location of the affected protein:
- Kidney Damage: Protein in the urine (proteinuria) often indicates kidney damage. ([References: Kidney Fund; MedlinePlus])
- Neurological Disorders: Protein misfolding plays a significant role in neurodegenerative diseases like Alzheimer's and prion diseases. The accumulation of misfolded proteins disrupts brain function and causes neuronal damage. ([References: NIA on Alzheimer's; NIH News Release June 11, 2009])
- Immune System Dysfunction: Damaged proteins can impair immune function, as seen in common variable immunodeficiency. ([Reference: PubMed 33995346])
