| Gene |
[LAMA5](/genes/lama5) |
| UniProt |
O15230 |
| PDB |
4AER |
| Mol. Weight |
400 kDa (alpha chain) |
| Localization |
Extracellular matrix (basement membranes) |
| Family |
Laminin family (extracellular glycoprotein) |
| Diseases |
[Alzheimer's Disease](/diseases/alzheimers), [Parkinson's Disease](/diseases/parkinsons-disease) |
Laminin subunit alpha-5 (LAMA5) is a key component of the extracellular matrix, forming the alpha chain of laminin-511 (α5β1γ1) and laminin-521 (α5β2γ1) heterotrimers. These laminins are major constituents of basement membranes in the brain, where they provide structural support and regulate neuronal migration, synapse formation, and blood-brain barrier integrity. LAMA5 has been implicated in Alzheimer's disease pathogenesis through its involvement in Aβ deposition and neuronal vulnerability.
LAMA5 is a large extracellular glycoprotein:
- N-terminal domains: Five LG (laminin G-like) domains for cell surface binding
- Long coiled-coil domain: Forms heterotrimer with beta and gamma chains
- C-terminal domains: Involved in cell adhesion and signaling
LAMA5 combines with LAMB1 or LAMB2 and LAMC1 to form laminin-511 or laminin-521.
In the nervous system:
- Basement membrane formation: Critical component of vascular and neuronal basement membranes
- Neuronal migration: Guides neuronal migration during development
- Synapse formation: Promotes excitatory synapse formation and maturation
- Blood-brain barrier: Maintains BBB integrity through perivascular basement membrane
- Axonal guidance: Provides guidance cues for growing axons
- LAMA5 accumulates in Aβ plaques
- Laminin-511/521 interact with Aβ, potentially promoting plaque formation
- Altered basement membrane composition in AD brains
- LAMA5 deficiency accelerates Aβ pathology in mouse models
- Role in Aβ clearance across the BBB
- Laminin expression altered in substantia nigra of PD patients
- Involved in dopaminergic neuron survival
- LAMA5 polymorphisms associated with PD risk in some populations
- Basement membrane remodeling during neuroinflammation
- LAMA5 degradation products as inflammation markers
Targeting LAMA5:
- Laminin-derived peptides to promote healthy neuronal function
- Gene therapy to restore basement membrane integrity
- LAMA5-binding agents for drug delivery
- Laminin in Alzheimer's disease pathology (Mohan et al., 2018)
- LAMA5 and synapse formation (Nakagawa et al., 2019)
- Basement membrane in neurodegeneration (Baumann et al., 2021)