Key Transcription Factors Linking Macular Degeneration and Alzheimer’s Disease

Alzheimer’s disease (AD) and age-related macular degeneration (AMD) have certain pathologic features in common. Chronic oxidative stress and neuroinflammation result in aggregate protein deposits, extracellular drusen in AMD, extracellular and intracellular amyloid in AD, and intracellular tau in AD, and mitochondrial proteosomal pathway damage in both. Along with risk factors: aging, smoking, hypertension, hypercholesterolemia, obesity, arteriosclerosis, unhealthy diet, chronic anticholinergic use, and latent herpetic infection, three transcription factors, NRF-2 (nuclear factor-erythroid 2) and NFKB (nuclear factor kappa B) which regulate cellular detoxification from oxidative stress and innate cellular immunity, respectively, and PGC-1α (peroxisome receptor gamma coactivator), which is the master of mitochondrial biogenesis and antioxidant control, seem to play a major role in disease progression of AMD and AD . Neuropathology and protein marker changes related to imbalances in NRF-2, NFKB, and PGC- 1α illustrate neurodegenerative and vision loses commensurate with NRF-2 and PGC-1α deficiencies and NFKB excess. Examining these transcription factors in more detail may provide insights into slowing the progression of AD and AMD.