Diseases Affecting the Cell Membrane: Mechanisms and Examples

Cell membrane disorders disrupt integrity, transport, signaling, or adhesion. Major categories:

1. Red Blood Cell Membranopathies

• Hereditary spherocytosis: Spectrin/ankyrin/band 3 defects → spherical RBCs → hemolysis.
• Hereditary elliptocytosis: Spectrin/protein 4.1 defects → elliptical RBCs.
• Paroxysmal nocturnal hemoglobinuria (PNH): PIG-A mutation → GPI-anchor deficiency → complement-mediated lysis.

2. Neuromuscular Junction Disorders

• Myasthenia gravis: Autoantibodies against AChR (postsynaptic membrane) → impaired neuromuscular transmission.
• Lambert-Eaton syndrome: Antibodies against presynaptic VGCC → reduced ACh release.

3. Channelopathies

• Cystic fibrosis: CFTR chloride channel defect → thick mucus, multi-organ disease.
• Long QT syndrome: Cardiac K⁺/Na⁺ channel mutations → arrhythmia.
• Episodic ataxias, myotonias: Neuronal/muscle channel mutations.

4. Metabolic/Storage Disorders Affecting Membranes

• Sickle cell disease: Hemoglobin S polymerizes → membrane rigidity, vaso-occlusion.
• Diabetes: Chronic hyperglycemia → glycation of membrane proteins, oxidative stress, microvascular damage.
• Lysosomal storage diseases (e.g., Niemann-Pick, Gaucher): Lipid accumulation disrupts membrane trafficking.

5. Neurodegenerative Membrane Pathology

• Alzheimer's: Amyloid-β oligomers disrupt synaptic membranes; tau mislocalization.
• Prion diseases: PrP^Sc aggregates in membrane microdomains.

6. Renal Membrane Disease

• Membranous nephropathy: Autoantibodies (anti-PLA2R) target podocyte membrane → subepithelial immune deposits → nephrotic syndrome.

7. Infectious Membrane Disruption

• Malaria: Plasmodium
• Bacterial toxins: Pore-forming (hemolysins), phospholipases.

Understanding membrane pathophysiology drives targeted therapies: eculizumab (PNH), CFTR modulators (CF), anti-PLA2R monitoring (membranous nephropathy).