Elizabeth Engel nee Benjamin-Rasmussen in her home; Silver Springs, Maryland Portraits Women

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Elizabeth Engel nee Benjamin-Rasmussen with her daughter Dorel Hall nee Engel in Elizabeth's home; Silver Springs, Maryland Portraits Family

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Hans Krakauer and Elizabeth Krakauer nee Gottschalk; Boston, New York. Portraits Couples

Photograph taken in front of the house in Boston, in upstate New York outside of Buffalo, where in 1939 they set up their private medical practice. After WWII, they built a new house next door.

Wedding portrait of Hans Krakauer and Elizabeth Godshaw (Gottschalk); Hannover, Germany. Portraits Couples

In the apartment on Ruemkorffstrasse that the Gottschalks occupied after being forced to sell their house.

Elizabeth Krakauer nee Gottschalk seated in a Oberprima (high school) chemistry laboratory; Sophienschule; Hannover, Germany.

This picture was taken during her last year of high school. The chemistry teacher, Professor Schmigielski was one of Elizabeth's favorite teachers.

Portrait of Elizabeth Krakauer nee Gottschalk with pigtails; Hannover, Germany.

This portrait shows Elizabeth with pig tails. In a defiant mood, she cut them off.

Freddy, Ursula, Elizabeth, Hal, Walter, and Kurt Gottschalk sharing a bed with their parents.

From left to right: Fred Gottschalk, grandma, Ursula Gottschalk, Elizabeth Gottschalk, grandpa, Hal Gottschalk, Walter Gottschalk, and Kurt Gottschalk

Walter, Freddy, Kurt and Elizabeth Gottschalk with their mother Therese Gottschalk nee Molling, and the maid on an easter egg hunt; Hannover, Germany.

From left to right: Walter Gottschalk, Therese Gottschalk nee Molling, Freddy Gottschalk, the maid, Kurt Gottschalk, and Elizabeth Gottschalk

Henny Molling with Therese, Hal, Kurt and Elizabeth Gottschalk at the swim club; Hannover, Germany.

From left to right: Therese Gottschalk, Hal Gottschalk, Kurt Gottschalk, Henny Molling; on the ground: Elizabeth Gottschalk

"Klo-Ku-Ba", Hans and Elizabeth Krakauer's first apartment in the basement of the Jewish Hospital; Hannover, Germany.

"Klo-Ku-Ba" the first apartment of Hans and Elizabeth in the basement of the Jewish Hospital in Hannover, Germany. The one room served as kitchen, bedroom, and bathroom which was shared by the other residents on the medical staff. Klo-Ku-Ba: Klosett, Kueche, Bad

Portrait of Elizabeth Krakauer nee Gottschalk with pigtails; Hannover, Germany.

This portrait shows Elizabeth with pig tails. In a defiant mood, she cut them off.

Portrait of the six Gottschalk children Walter, Ursula, Freddy, Hal, Elizabeth and Kurt in garden; Hannover, Germany. Portraits Children

Front row from left to right: Walter, Ursula, and Freddy; back row from left to right: Hal, Elizabeth, and Kurt Godshaw; picture was probably taken in their backyard on Seelhorststrasse in Hannover, Germany

Studio Portrait of Elizabeth, Kurt and Hal Godshaw (Gottschalk).

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Portrait of the six Gottschalk children Walter, Ursula, Freddy, Hal, Elizabeth and Kurt in garden; Hannover, Germany. Portraits children

Front row from left to right: Walter, Ursula, and Freddy; back row from left to right: Hal, Elizabeth, and Kurt Godshaw; picture was probably taken in their backyard on Seelhorststrasse in Hannover, Germany

Cathepsin D Deficiency - Molecular and Cellular Mechanisms of Neurodegeneration

Cathepsin D (CTSD) is a lysosomal protease, the deficiency of which is fatal and associated with neurodegeneration. CTSD knock-out mice, which die at the age of four weeks, show intestinal necrosis, loss of lymphoid cells and moderate pathological changes in the brain. An active-site mutation in the CTSD gene underlies a neurodegenerative disease in newborn sheep, characterized by brain atrophy without any changes to visceral tissues. The CTSD deficiences belong to the group of neuronal ceroid-lipofuscinoses (NCLs), severe neurodegenerative lysosomal storage disorders. The aim of this thesis was to examine the molecular and cellular mechanisms behind neurodegeneration in CTSD deficiency. We found the developmental expression pattern of CTSD to resemble that of synaptophysin and the increasing expression of CTSD to coincide with the active period of myelination in the rat brain, suggesting a role for CTSD in early rat brain development. An active-site mutation underlying the congenital ovine NCL not only affected enzymatic activity, but also changed the stability, processing and transport of the mutant protein, possibly contributing to the disease pathogenesis. We also provide CTSD deficiency as a first molecular explanation for human congenital NCL, a lysosomal storage disorder, characterized by neuronal loss and demyelination in the central nervous system. Finally, we show the first evidence for synaptic abnormalities and thalamocortical changes in CTSD-deficient mice at the molecular and ultrastructural levels. Keywords: cathepsin D, congenital, cortex, lysosomal storage disorder, lysosome, mutation, neurodegeneration, neuronal ceroid-lipofuscinosis, overexpression, synapse, thalamus