Biomedical Engineering Reference
In-Depth Information
7.3 Membrane Topology and Alzheimer's Disease
The cause of familial Alzheimer's disease has been identified as being due to muta-
tions in genes (for general understanding see the Refs. [ 8 , 14 , 51 ]). A large number
of mutations spread throughout the structures of proteins presenilin 1 and 2 which are
linked to Alzheimer's disease [ 7 , 24 ]. The protein presenilin 1 is an integral mem-
brane protein. Membrane topology of Alzheimer's disease-related presenilin 1 was
explained in detail in the Ref. [ 30 ]. Presenilin 1 and 2, which are highly homologous
to each other, were reported to be mainly localized in the membranes of intracellular
compartments such as the endoplasmic reticulum. A convincing membrane topol-
ogy model for both of these presenilins 1 and 2 was proposed. Due to the membrane
association of the genes that are responsible for Alzheimer's disease, it can be pre-
dicted that membrane structure and mechanisms may also be affected in Alzheimer's
disease patients. Conversely, membrane topology may also have a substantial role to
play in both the onset and therapy for Alzheimer's disease. However, a rather insignif-
icant number of investigations have so far been undertaken to understand this effect.
Some progress has been made in developing theories that explain how Alzheimer's
disease causes the death of brain cells [ 12 ], but a molecular mechanism is yet to be
discovered. Similarly, the role of the membrane, an important cellular compartment,
is yet to be discovered through membrane-based research by associating proteins
like presenilins 1 and 2, amyloid precursor protein, etc.
7.4 Alcohol-Related Diseases, Their Effects on Lipid Membranes
and Possible Treatments, Focusing on Membrane Effects
Alcohol is a social drink. Many people drink alcohol occasionally, many do it daily
and for many drinking is an addiction. Numerous studies suggest that alcohol has
different effects on the human body, depending on the amount and frequency of
drinking, as well as the physiology of the individual. Heavy drinkers are found, in
large proportion, to face serious liver disease. Liver injury may be caused by direct
toxicity of metabolic byproducts of alcohol, as well as by inflammation induced
by these byproducts [ 26 ]. In addition to liver problems, many other types of health
issues may appear due to alcohol use beyond the tolerance limit, which is not yet
precisely determined. Brain damage, cancers (especially of the mouth and throat),
lung infections, high blood pressure, stomach ulcers, colon cancer, osteoporosis (by
interfering with the body's ability to absorb calcium), body and skin dehydration,
sexual and mental health issues, etc. may develop as a result of drinking alcohol
in excess. Detailed analysis of all these alcohol-related diseases suggests that the
cellular environment is somehow adversely affected by the effects of alcohol. We
address some of the cell membrane effects of alcohol below.
Terama et al. [ 44 ] reported that the influence of ethanol on the lateral pressure
profile of a lipid bilayer is prominent, reaching several hundred atmospheres. Ethanol
 
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