Name of disease

Cause of disease/Info

serious neurological disease characterized by severe seizures and blindness.

Inability to synthesize gangliosides

severe muscular tremors and eventual paralysis in MICE

Inability to synthesize galactocerebroside

Zellweger syndrome

Patients with Zellweger syndrome lack peroxisomal enzymes due to defects in translocation of proteins from the cytoplasm into the peroxisome. ZS can arise from mutations in at least 12 different genes, all encoding proteins involved in the uptake of peroxisomal enzymes from the cytosol.

Important*

A variety of disorders result from abnormalities in mitochondria structure and function; most are characterized by degeneration of muscle or brain tissue, both use large amounts of ATP.

atherosclerotic plaque

(atherosclerosis)

LDL deposition leads to plaques on inner lining of blood vessels.

LDL synthesis can be blocked by STATINS which block HMG CoA reductase, a key enzyme in the synthesis of cholesterol.

Adrenoleukodydstrophy (X-ALD)

 is caused by lack of a peroxisomal enzyme, leading to fatty acid accumulation in the brain and destruction of the myelin sheath of nerve cells.

Lysosomal storage disorders

Most importantly:

TAY-SACHS DISEASE

Lysosomal storage disorders result from the absence of specific lysosomal enzymes thus allowing undigested material to accumulate.

Tay-Sachs disease results from a deficiency in an enzyme responsible for degrading gangliosides, a major component of cell membranes

Important**

Several diseases are linked to mutations in lysosomal membrane proteins that impair transport of substances from the lysosomal lumen to the cytosol.

Gaucher’s disease

Treated by Cerezyme

Note*

An abnormally high level of phosphorylation of one particular MAP, called tau, has been implicated in Alzheimer’s disease

 Amyotrophic Lateral Sclerosis (ALS).

Defects in both anterograde and retrograde transport have been linked to neurological diseases

 microcephaly

Genetic defects in centrosome-associated proteins cause microcephaly, because neuron proliferation and migration is sensitive to loss of centrosome function.

Kidney failure in long-term diabetics

may result from an abnormal thickening of the basement membranes surrounding the glomeruli.

decreased skin elasticity and increased bone brittleness among the elderly.

 cross-linking between lysine and hydroxylysine residues on adjacent molecules. This cross-linking process continues through life

Note**

Inappropriate MMP activity has been implicated in arthritis, tooth and gum disease, formation of blood clots and heart attack, and tumor progression.

autoimmune disease bullous pemphigoid

antibodies are made towards proteins present in these adhesive structures. These auto-antibodies cause the epidermal layer to lose attachment to the underlying basement membrane and result in severe skin blistering.

Epidermolysis bullosa

results from genetic alterations in hemidesmosomal proteins, including the α6 or β4 integrin subunit, collagen VII, or laminin-5.

Cholera toxin

 pertussis virulence

Note**

Reduced or elevated apoptosis is linked to several human diseases: Cancer; Parkinson’s, Alzheimer’s, and Huntington’s diseases; Diabetes type I